Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.

Involvement of the Olfactory Apparatus by Gliomas.

The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to involve the olfactory apparatus. Through a Health Insurance Portability and Accountability Act-compliant retrospective review of the institutional teaching files and brain MR imaging reports spanning 10 years, we identified 12 cases of gliomas involving the olfactory bulbs and tracts, including 6 cases of glioblastoma, 2 cases of anaplastic oligodendroglioma, and 1 case each of pilocytic astrocytoma, diffuse (grade II) astrocytoma, anaplastic astrocytoma (grade III), and diffuse midline glioma. All except the pilocytic astrocytoma occurred in patients with known primary glial tumors elsewhere. Imaging findings of olfactory tumor involvement ranged from well-demarcated enhancing masses to ill-defined enhancing infiltrative lesions to nonenhancing masslike FLAIR signal abnormality within the olfactory tracts. Familiarity with the imaging findings of glioma involvement of the olfactory nerves is important for timely diagnosis and treatment of recurrent gliomas and to distinguish them from other disease processes.

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

CONTEXT: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. OBJECTIVE: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. METHODS: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. RESULTS: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. CONCLUSIONS: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Meningiomas del surco olfatorio: consideraciones del abordaje endonasal endoscópico extendido transcribiforme / Olfactory groove meningiomas: considerations of the extended endoscopic endoscopic approach transcribiform

Los meningiomas del surco olfatorio representan el 10 por ciento de los meningiomas intracraneales, se originan de la lámina cribosa del etmoides, la sutura fronto-esfenoidal y el plano esfenoidal. Son tumores en su mayoría benignos y potencialmente curables, la recurrencia ocurre en grado variable siendo el grado de resección quirúrgica el predictor más importante de recurrencia. En este artículo se exponen los resultados alcanzados con el abordaje endonasal endoscópico extendido transcribiforme en pacientes con meningiomas del surco olfatorio en el servicio de neurocirugía del hospital clínico quirúrgico Hermanos Ameijeiras. La serie fue de 12 pacientes donde la cefalea, la anosmia y los trastornos neuropsicológicos fueron los síntomas predominantes. Los tumores tuvieron un tamaño ≥ a 6 cm en el 50 por ciento de los casos y con el abordaje endonasal endoscópico extendido transcribiforme se alcanzó una resección total con Simpson I en el 92 por ciento de los enfermos. Los límites del abordaje endonasal endoscópico en la fosa anterior se encuentran en constante extensión, siendo el abordaje endonasal endoscópico extendido transcribiforme la opción ideal y prometedora para los pacientes con Meningiomas del surco olfatorio.

Olfactory groove meningiomas represent 10 percent of intracranial meningiomas, originate from cribriform plate of ethmoid, frontal and sphenoid suture and the sphenoid plane. They are mostly benign and potentially curable tumors, the recurrence occurs in varying degree and the extent of surgical resection is the most important predictor of this recurrence. This article presents the results achieved with the transcribiform extended endoscopic endonasal approach in patients with meningiomas of olfactorygroove in neurosurgery department of the “Hermanos Ameijeiras” hospital. The series was of 12 patients where headache, anosmia, and neuropsychological disorders were the predominant symptoms. The tumors had a size ≥ 6 cm on 50 percent of the cases and with transcribiform extended endoscopic endonasal approach was reached total removal in 92 percent (Simpson I) of the patients. The limits of endoscopic endonasal approach for anterior fossa are in constant expansion, being the transcribiform extended endoscopic endonasal approach the ideal and promising option for patients with olfactory groove meningiomas.

Age effects on the nucleus of the lateral olfactory tract of the rat.

The olfactory deficits that occur during aging influence the quality of life and have been regarded as a risk factor for malnutrition in the elderly. The nucleus of the lateral olfactory tract (nLOT) is a cortical nucleus of the pallial amygdala that has been implicated in feeding behavior. Here we present quantitative data on the anatomy of the nLOT in the adult rat and on the effects of age on its structure and neurochemistry. Total neuron numbers, neuronal volumes, and volumes of layers 1-3 of the nLOT were estimated in adult and old male rats using stereological techniques. We also estimated the total number of interneurons expressing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), and the numerical density of the nLOT cholinergic varicosities. Our data show that aging is associated with a reduction of the total neuron numbers in the nLOT, due to cell loss in layers 2 and 3. There were no age-related variations in neuronal volumes. Similarly, the volume of the nLOT was unchanged in aged rats, except in layer 3 where it was reduced. The numerical density of cholinergic varicosities was also unchanged in aged rats. Conversely, the total numbers of NPY- and VIP-immunoreactive neurons were reduced by 55% and 30%, respectively, in aged rats. These findings include the nLOT in the list of cortical olfactory structures susceptible to aging and raise the possibility that the age-related changes that occur in the nLOT might contribute for the decline in olfactory functions reported in normal aging.

Unilateral Tailored Fronto-Orbital Approach for Giant Olfactory Groove Meningiomas: Technical Nuances.

OBJECTIVE: Giant olfactory groove meningiomas (maximum diameter ≥6 cm) remain a surgical challenge. Historically, extensive anterior and antero-lateral approaches have been the primary approaches for removal of such large tumors with limitations and morbidity pertaining to each approach. Herein, the authors describe a minimally invasive, unilateral, tailored fronto-orbital approach for resection of these complex lesions with an emphasis on preservation of the anterior cerebral arteries and olfactory nerves. METHODS: A 4-stage approach using neuronavigation is performed: 1) predefined corridor, 2) identification of the ipsilateral anterior cerebral artery, 3) postdefined corridor, and 4) tumor base. The details of this approach are described below in a stepwise fashion and supplemented by a sample of 3 cases utilizing this technique. RESULTS: In the 3 representative cases in which this technique was used, gross total resection was achieved without injury to any of the adjacent neurovascular structures. Significant sellar extension can be resected through a second stage endoscopic endonasal approach. CONCLUSION: Giant olfactory groove meningiomas (≥6 cm) can be safely and completely resected with this 4-stage, unilateral fronto-orbital technique. Furthermore, early identification and preservation of the adjacent critical neurovascular structures can be achieved. This technique avoids the inherent limitations and morbidity associated with the more classic pterional and bifrontal approaches respectively while minimizing normal tissue disruption.

Evaluation of post-traumatic anosmia with MRI and chemosensory ERPs.

Magnetic resonance imaging (MRI) and chemosensory event-related potentials (ERPs) are important methods to evaluate olfactory function, but there is lack of study to explore the application of MRI and chemosensory ERPs in the patients with traumatic anosmia. The data of 26 post-traumatic anosmic patients and 21 healthy controls were retrospectively surveyed; olfaction and olfactory pathway of all participants were measured clinically using the T&T olfactometer, the Sniffin' Sticks, chemosensory ERPs and MRI. All patients were anosmic based on complaints and clinical examinations. In five patients, the olfactory bulb volume was significantly lower than control group. In 18 patients, the olfactory sulcus (OS) depth was similar to control group, but all the participants had a deeper right OS (right = 7.79 ± 1.31, left = 7.06 ± 1.44, p < 0.01). Olfactory ERPs (oERPs) could be evoked in 17 patients, but these signals showed longer latencies and lower amplitude than controls in the N1 (latency p < 0.05, amplitude p < 0.01) and P2 (latency p < 0.01, amplitude p < 0.05) waves. Nine traumatic anosmic patients had no identifiable oERPs; most of them had olfactory center injury. Trigeminal ERPs were detected in all anosmic patients and controls; patients had longer latencies for N1 (p < 0.05) and P2 (p < 0.05) waves, while there was no similar change in amplitude. Older subjects had smaller OB volume and OS depth. Closed head injury could induce anosmia; the severity extent, injury site and subsequent consciousness are related to the olfaction. oERP is the gold standard for olfactory subjective examination; MRI could indicate the lesions on the olfactory pathway and reflect the possibility of detectable oERPs.

p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish.

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium.

Surgical anatomy of endoscope-assisted approaches to common aneurysm sites.

BACKGROUND: The endoscope is being introduced as an adjuvant to improve visualization of certain areas in open cranial surgery. OBJECTIVE: To describe the endoscopic anatomy of common aneurysm sites and to compare it with the microsurgical anatomy. METHODS: Pterional, anterior interhemispheric, and subtemporal approaches to the most common aneurysm sites were examined in cadaveric heads under the surgical microscope and with the endoscope. RESULTS: The endoscopic view, particularly with the angled endoscopes, provides a significant improvement compared with the microscopic view, especially for poorly visualized sites such as the medial aspect of the supraclinoid carotid artery and its branches, the area below the anterior perforated substance and optic tract, and the carotid and basilar bifurcations. The endoscope aided in the early visualization of perforating branches at each aneurysm site except the middle cerebral artery. Small-diameter optics (2.7 mm) provided greater space for dissection and less potential for tissue damage in narrow places, whereas the larger 4-mm diameter optics provided better visualization and less panoramic distortion. The positioning of the endoscope for each aneurysm site is reviewed. CONCLUSION: The endoscope provides views that complement or improve the microscopic view at each aneurysm site except the middle cerebral artery. Endoscopy training and a thorough knowledge of endoscopic vascular anatomy are essential to safely introduce endoscopic assistance in vascular surgery.

Olfactory system and demyelination.

Within the central nervous system, the olfactory system represents one of the most exciting scenarios since it presents relevant examples of long-life sustained neurogenesis and continuous axonal outgrowth from the olfactory epithelium with the subsequent plasticity phenomena in the olfactory bulb. The olfactory nerve is composed of nonmyelinated axons with interesting ontogenetic interpretations. However, the centripetal projections from the olfactory bulb are myelinated axons which project to more caudal areas along the lateral olfactory tract. In consequence, demyelination has not been considered as a possible cause of the olfactory symptoms in those diseases in which this sense is impaired. One prototypical example of an olfactory disease is Kallmann syndrome, in which different mutations give rise to combined anosmia and hypogonadotropic hypogonadism, together with different satellite symptoms. Anosmin-1 is the extracellular matrix glycoprotein altered in the X-linked form of this disease, which participates in cell adhesion and migration, and axonal outgrowth in the olfactory system and in other regions of the central nervous system. Recently, we have described a new patho-physiological role of this protein in the absence of spontaneous remyelination in multiple sclerosis. In the present review, we hypothesize about how both main and satellite neurological symptoms of Kallmann syndrome may be explained by alterations in the myelination. We revisit the relationship between the olfactory system and myelin highlighting that minor histological changes should not be forgotten as putative causes of olfactory malfunction.

Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.

Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States.

Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.

Excessive activation of mTOR in postnatally generated granule cells is sufficient to cause epilepsy.

The dentate gyrus is hypothesized to function as a "gate," limiting the flow of excitation through the hippocampus. During epileptogenesis, adult-generated granule cells (DGCs) form aberrant neuronal connections with neighboring DGCs, disrupting the dentate gate. Hyperactivation of the mTOR signaling pathway is implicated in driving this aberrant circuit formation. While the presence of abnormal DGCs in epilepsy has been known for decades, direct evidence linking abnormal DGCs to seizures has been lacking. Here, we isolate the effects of abnormal DGCs using a transgenic mouse model to selectively delete PTEN from postnatally generated DGCs. PTEN deletion led to hyperactivation of the mTOR pathway, producing abnormal DGCs morphologically similar to those in epilepsy. Strikingly, animals in which PTEN was deleted from ≥ 9% of the DGC population developed spontaneous seizures in about 4 weeks, confirming that abnormal DGCs, which are present in both animals and humans with epilepsy, are capable of causing the disease.

Long-term effects of estradiol replacement in the olfactory system.

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol treatment increased the number of mature neurons in the OE and glomerular synaptophysin in both genotypes, but the magnitude of increase was greater in the WT than in the KO mice. These data suggest that estrogen and apoE act synergistically to minimize the loss of mature sensory neurons and synapses following ovariectomy.

An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation.

The glomeruli are the first synaptic relay on the olfactory pathway and play a basic role in smell perception. Glomerular degeneration occurs in humans with age and in Alzheimer's disease (AD). The glomeruli heavily express ß-amyloid precursor protein (APP), ß-secretase (BACE1) and γ-secretase complex. However, extracellular ß-amyloid peptide (Aß) deposition occurs fairly rarely at this location in postmortem pathological studies. We sought to explore age-related glomerular changes that might link to alteration in amyloidogenic proteins and/or plaque pathogenesis in transgenic models of AD and humans. Focally increased BACE1 immunoreactivity (IR) in the glomerular layer was identified in several transgenic models, and characterized systematically in transgenic mice harboring five familiar AD-related mutations (5XFAD). These elements were co-labeled with antibodies against APP N-terminal (22C11) and Aß N-terminal (3D6, 6E10) and mid-sequence (4G8). They were not co-labeled with two Aß C-terminal antibodies (Ter40, Ter42), nor associated with extracellular amyloidosis. These profiles were further characterized to be most likely abnormal olfactory nerve terminals. Reduced glomerular area was detected in 6-12-month-old 5XFAD mice relative to non-transgenic controls, and in aged humans relative to young/adult controls, more robust in AD than aged subjects without cerebral amyloid and tau pathologies. The results suggest that olfactory nerve terminals may undergo age-related dystrophic and degenerative changes in AD model mice and humans, which are associated with increased labeling for amyloidogenic proteins but not local extracellular Aß deposition. The identified axon terminal pathology might affect neuronal signal transmission and integration at the first olfactory synaptic relay.

Permanent anosmia and ageusia after resection of a left temporoinsular low-grade glioma: anatomofunctional considerations.

Five percent of the general population has olfactory or gustatory disorders, although most do not complain about it. However, in some cases, these symptoms can be disabling and may affect quality of life. Anosmia was reported as a possible complication following head injury and neurosurgical procedures, particularly after the resection of tumors located in the anterior fossa and the treatment of aneurysms in the anterior circulation. Nonetheless, in all of these situations, olfactory dysfunction could be explained by damage to the peripheral olfactory system. Here, the authors report a case of complete anosmia associated with ageusia following awake resection of a low-grade glioma involving the left temporoinsular region, with no recovery during a follow-up of 3 years. The frontal lobe was not retracted, and the olfactory tract was not visualized during surgery; therefore, postoperative anosmia and ageusia are likely explained by damage to the cortex and central pathways responsible for these senses. The authors suggest that the patient might have had a subclinical right hemianosmia before surgery, which is a common condition. After resection of the central structures critical for smell and taste processing in the left hemisphere, the patient could have finally had bilateral and complete olfactory and gustatory loss. This is the first known report of permanent anosmia and ageusia following glioma surgery. Because these symptoms might have been underestimated, more attention should be devoted to olfaction and taste, especially with regard to possible subclinical preoperative deficit.

NCAM2/OCAM/RNCAM: cell adhesion molecule with a role in neuronal compartmentalization.

Neural cell adhesion molecules 2 (NCAM2/OCAM/RNCAM), is a paralog of NCAM1. The protein exists in a transmembrane and a lipid-anchored isoform, and has an ectodomain consisting of five immunoglobulin modules and two fibronectin type 3 homology modules. Structural models of the NCAM2 ectodomain reveal that it facilitates cell adhesion through reciprocal interactions between the membrane-distal immunoglobulin modules. There are no known heterophilic NCAM2 binding partners, and NCAM2 is not glycosylated with polysialic acid, a posttranslational modification known to be a major modulator of NCAM1-mediated processes. This suggests that NCAM2 has a function or mode of action distinctly different from that of NCAM1. NCAM2 is primarily expressed in the brain, where it is believed to stimulate neurite outgrowth and to facilitate dendritic and axonal compartmentalization.

Solitary olfactory schwannoma without olfactory dysfunction: a new case report and literature review.

Schwannomas are rare and seldom extend into the anterior cranial fossa. Herein, we report a case of schwannoma arising from the olfactory groove in a 16-year-old girl who presented with generalized seizures without olfactory dysfunction or other neurologic deficits. Computerized tomography (CT) scan showed a large mass with abundant calcification located in the olfactory groove, which was confirmed as a schwannoma by histology and totally resected via basal subfrontal approach. The presentation, imaging findings and histogenesis of the tumor are discussed along with a review of the pertinent literature.

Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's ß-amyloidosis mouse model.

The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of ß-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-ß (Aß) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB-PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Aß-dependent, because liver-X receptor agonist treatment to promote Aß degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior.

Giant olfactory groove meningiomas: extent of frontal lobes damage and long-term outcome after the pterional approach.

OBJECTIVE: The treatment of giant olfactory groove meningiomas (OGMs; maximum diameter ≥ 6 cm) poses special problems and represents a surgical challenge. We discuss the long-term results in a series of 18 patients with giant OGMs and report our experience on a global strategy encompassing the pterional approach to manage the lesion and an extended transbasal approach to treat recurrences. METHODS: Between February 1991 and December 2007, 18 patients with giant OGMs were surgically managed via a pterional craniotomy. Postoperative follow-up imaging was obtained at one, six, and 12 months and then yearly. In preoperative images, data from tumor volume were assessed. The volume of the residual right frontal porencephalic cave (ipsilateral to the operative side) was compared with the volume of the porencephalic cave measured in the left frontal lobe (internal control) in each case. Comparison between porencephalic cave and the original tumor volume for each side was also performed. RESULTS: At the first operation in 17 of 18 patients (94.4%), the tumor resection was accomplished by a complete macroscopic lesion removal and coagulation of its dural attachment (Simpson grade II). In one patient, a Simpson grade V resection was obtained. The mean follow-up was 93.5 months, ranging from 12 to 214 months. Recurrences were observed in three patients (16.7%) at 103, 102, and 128 months, respectively, from the time of the first operation. These patients were operated on via an extended subfrontal transbasal approach accomplishing a complete (Simpson grade I) resection. No death occurred. The visual deficit improved in seven of 13 patients (53.8%), remained stable in five (38.5%), and worsened in one patient (7.7%). Overall, 17 of 18 patients (94.4%) had a good outcome and returned to their previous occupations. All the tumors presented with a symmetrical growth pattern. The mean meningioma volume was 23.51 ± 1.62 cm(3) for the right portion of the tumor and 23.04 ± 1.35 cm(3) for the left portion. The mean residual porencephalic volume was significantly smaller in the left frontal lobe (mean value 5.7 mL) than in the right frontal lobe (mean value 16.6 mL; P < 0.05). The mean residual porencephalic volume was significantly smaller than the tumor volume both in the left (P < 0.01) and in the right side (P < 0.05). CONCLUSION: The pterional-transsylvian approach provides two major advantages: first, it minimizes morbidity and mortality through an early neurovascular control and by limiting parenchymal damage as demonstrated by a quantitative analysis; second it is associated with low recurrence rate at a long-term follow-up.