Cranio-Orbital and Orbitocranial Approaches to Orbital and Intracranial Disease: Eye-Opening Approaches for Neurosurgeons.

Orbital approaches for targeting intracranial, orbital, and infratemporal disease have evolved over the years in an effort to discover safe, reliable, effective, and cosmetically satisfying surgical corridors. The surgical goals of these approaches balance important factors such as proximity of the lesion to the optic nerve, the degree of anticipated manipulation and required space for surgical maneuverability, and the type of disease. The authors provide a comprehensive review of the most commonly used periorbital approaches in the management of intra- and extracranial disease, with emphasis on the advantages and limitations of each approach.

Malignant carotid body tumor presenting with myelopathy: case report.

Malignant carotid body tumors are rare, with spread of the tumor mostly noted in regional lymph nodes. Vertebral metastases are an exceedingly rare presentation, only reported in isolated case reports, and present a diagnostic and management challenge. A case of widespread vertebral metastasis, presenting with myelopathy, from a carotid body tumor is discussed in this paper, along with management strategies.

ATP-site binding inhibitor effectively targets mTORC1 and mTORC2 complexes in glioblastoma.

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding inhibitor PP242, would effectively suppress GBM growth and dissemination as compared to an allosteric binding inhibitor of mTOR. GBM cells treated with PP242 demonstrated significantly decreased activation of mTORC1 and mTORC2, as shown by reduced phosphorylation of their substrate levels, p70 S6K(Thr389) and AKT(Ser473), respectively, in a dose-dependent manner. Furthermore, insulin induced activation of these kinases was abrogated by pretreatment with PP242 as compared with rapamycin. Unlike rapamycin, PP242 modestly activates extracellular regulated kinase (ERK1/2), as shown by expression of pERK(Thr202/Tyr204). Cell proliferation and S-phase entry of GBM cells was significantly suppressed by PP242, which was more pronounced compared to rapamycin treatment. Lastly, PP242 significantly suppressed the migration of GBM cells, which was associated with a change in cellular behavior rather than cytoskeleton loss. In conclusion, these results underscore the potential therapeutic use of the PP242, a novel ATP-competitive binding inhibitor of mTORC1/2 kinase, in suppression of GBM growth and dissemination.

Malignant fungal infection of the cavernous sinus: case report.

Intracranial spread of fungal infection is a life-threatening condition that usually affects immunocompromised patients. Here the authors present a case of biopsy-proven Aspergillus fumigatus infection of the paranasal sinuses in an immunocompetent patient with documented spread to the orbit, cavernous sinus, and petrous apex despite medical antifungal treatment. As a life-saving treatment, cavernous sinus resection with external carotid artery-middle cerebral artery bypass was performed. The authors discuss the literature regarding the intracranial spread of paranasal sinus fungal infections in immunocompetent patients and management strategies.

Rescue microsurgery with bypass and stent removal following Pipeline treatment of a giant internal carotid artery terminus aneurysm.

We report the microsurgical rescue and removal of a Pipeline stent embolization of a giant internal carotid artery terminus aneurysm. After the initial placement of a Pipeline Embolization Device (PED), it migrated proximally to the cavernous carotid with the distal end free in the middle of the aneurysm, resulting in only partial aneurysm neck coverage. The patient underwent microsurgical rescue with trapping, bypass, and opening of the aneurysm with PED removal. The vessel remained patent in the proximal segment previously covered by the Pipeline stent. Microsurgical rescue for definitive aneurysm treatment with PED removal can be safe and effective for aneurysms unsuccessfully treated with PED.

Surgical management of traumatic frontal sinus fractures: Case series from a single institution and literature review.

BACKGROUND: Neurosurgeons are frequently involved in the management of patients with traumatic frontal sinus injury; however, management options and operative techniques can vary significantly. In this study, the authors review the current literature and retrospectively review the clinical series at a single tertiary referral center. METHODS: After Institutional Review Board approval, the medical records and computed tomographic (CT) imaging of patients whose traumatic frontal sinus fractures were treated surgically at the University of Utah were retrospectively reviewed. Demographic information, mechanism of injury, associated injuries, operative technique, and pattern of injury on CT were analyzed. RESULTS: Between 2000 and 2012, 33 patients underwent successful cranialization of the frontal sinus following traumatic injury. The material used to obliterate the sinus varied. No patients required immediate or delayed reoperation. Nasofrontal outflow tract obstruction, the importance of which has been emphasized in the plastic surgery literature, was apparent on either initial or retrospective review of the available CT imaging in 96%. CONCLUSIONS: In this series, we successfully surgically treated 33 patients with frontal sinus fractures. The presence of cerebrospinal fluid leak, nasofrontal outflow tract injury, associated depressed skull fractures, and subsequent formation of communicating pathways and infection must be considered when constructing a treatment plan. The goals of treatment should be: (i) surgical repair of the defect and elimination of the conduit from the intracranial space to the outside and (ii) elimination of any cerebrospinal fluid pressure gradient that may develop across the surgical repair. We present a treatment algorithm focusing on the presence of nasofrontal outflow tract injury/obstruction, cosmetic deformity, and cerebrospinal fluid leak.

The genetic basis of intradural spinal tumors and its impact on clinical treatment.

Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.

Left pterional craniotomy for thrombectomy and clipping of ruptured left MCA giant aneurysm.

Giant aneurysms present a challenge to cerebrovascular surgeons on many fronts. These lesions have significant mass effect on surrounding tissues and are often partially thrombosed with thickened or calcified walls; these difficulties are amplified in cases of subarachnoid hemorrhage. The treatment of these lesions often requires debulking or resection of the aneurysm with or without trapping and bypassing the aneurysm segment. The case presented is of a man with a ruptured giant left middle cerebral artery (MCA) aneurysm presenting with seizure. The treatment of this giant aneurysm involves dissection, opening and internal evacuation including the use of ultrasonic aspiration, resection, and clipping. The patient was given aspirin preoperatively in preparation for possible superficial temporal artery-MCA or saphenous vein bypass if clipping was not possible. Vessel patency was evaluated using intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. Postoperatively, the patient was neurologically intact. At 1 year his modified Rankin Scale is 1, with his only symptom being intermittent headache. The video can be found here: http://youtu.be/8dimNdiIObE .

Retrograde cysto-myelogram: Case Report.

BACKGROUND: In the scenario of blunt trauma with suspected bladder injury, conventional retrograde cystography is the gold standard for accurate diagnosis. CASE DESCRIPTION: The authors report the case of a 54-year-old patient who presented with pelvic and sacral fractures and a ruptured bladder after being hit by a vehicle. A retrograde computed tomography cystogram demonstrated extraperitoneal extravasation of the contrast agent, which traversed violated sacral nerve roots, resulting in contrast entering the subarachnoid space at the left sacral ala predominantly through the left L5 and S1 nerve roots. CONCLUSIONS: This is the first known report of an accidental myelogram imaging performed through a retrograde cystogram.

Surgical management of a transosseous meningioma with invasion of torcula, superior sagittal sinus, transverse sinus, calvaria, and scalp.

BACKGROUND: Meningiomas involving both intradural and extradural structures are rare tumors. We report the complete resection of a massive complex transosseous meningioma that had invaded the torcula, superior sagittal sinus, occipital bone, and scalp. CASE DESCRIPTION: A 48-year-old male presented after 3 days of worsening headaches and blurry vision. Preoperative imaging demonstrated an 11 × 5-cm extra-axial mass that avidly enhanced with gadolinium in the region of the torcula. Angiography demonstrated occlusion of the involved portions of the superior sagittal sinus, torcula, and proximal left transverse sinus. Cortical drainage occurred via the veins of Labbι and deep drainage via an occipital sinus. Using image-guided stereotaxy, a wide-excision scalp resection and craniectomy with sinus exploration was planned for complete tumor removal. Parasitized cortical veins were preserved. Occluded portions of the superior sagittal sinus and left transverse sinus were resected along with the invaded parts of the falx and tentorium. The walls of the straight sinus, torcula, and right transverse sinus were repaired primarily to facilitate deep drainage. A latissimus dorsi free flap was used to reconstruct the scalp defect. Routine follow-up magnetic resonance imaging (MRI) at 18 months demonstrated no evidence of recurrence or regrowth. CONCLUSIONS: This case illustrates the importance of identifying aberrant venous drainage pathways when considering ligation and resection of major sinuses and discusses the management of calvarial and scalp invasion.

Motion-related vascular abnormalities at the craniocervical junction: illustrative case series and literature review.

The craniocervical junction (CCJ) functions within a complicated regional anatomy necessary to protect and support vital neurovascular structures. In select instances, vascular pathology can be attributed to this complicated interplay of motion and structure found within this narrow space. The authors report 3 cases of complex vascular pathology related to motion at the CCJ and detail the management of these cases. Two cases involved posterior circulation vascular compression syndromes, and one case involved a vascular anomaly and its relation to aneurysm formation and rupture. The patient in Case 1 was a 66-year-old man with a history of syncopal episodes resulting from the bilateral vertebral artery becoming occluded when he rotated his head. Successful microsurgical decompression at the skull base resulted in patent bilateral vertebral artery V3 segments upon head movement in all directions. The patient in Case 2 was a 53-year-old woman who underwent elective resection of a right temporal meningioma and who experienced postoperative drowsiness, dysphagia, and mild right-arm ataxia. Subsequent MRI demonstrated bilateral posterior inferior cerebel-lar artery (PICA) strokes. Cerebral angiography showed a single PICA, of extradural origin, supplying both cerebellar hemispheres. The PICA exhibited dynamic extradural compression when the patient rotated her head; the bilateral PICA strokes were due to head rotation during surgical positioning. In Case 3, a 37-year-old woman found unconscious in her home had diffuse subarachnoid hemorrhage and evidence of a right PICA aneurysm. A right far-lateral craniectomy was performed for aneurysm clipping, and she was found to have a dissecting aneurysm with an associated PICA originating extradurally. There was a shearing phenomenon of the extradural PICA along the dura of the foramen magnum, and this microtraumatic stress imposed on the vessel resulted in a dissecting aneurysm. This series of complex and unusual cases highlights the authors' understanding of vascular pathology of the CCJ and its management.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma.

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

Far-lateral approach for surgical treatment of fusiform PICA aneurysm.

Ruptured fusiform posterior inferior cerebellar artery (PICA) aneurysms can be technically challenging lesions. Surgeons must be ready to employ a variety of strategies in the successful treatment of these aneurysms. Strategies include complex clip techniques including clip-wrapping or trapping and revascularization. The case presented here is of a man with subarachnoid hemorrhage from a fusiform ruptured PICA aneurysm. The technique demonstrated is a far-lateral approach and a clip-wrap technique using muslin gauze. The patient was given aspirin preoperatively in preparation for possible occipital-PICA bypass if direct repair was not feasible. It is the authors' preference to perform direct vessel repair as a primary goal and use bypass techniques when this is not possible. Vessel patency was evaluated after clip-wrapping using intraoperative Doppler. Intraoperative somatosensory and motor evoked potential monitoring is used in such cases. The patient recovered well. The video can be found here: http://youtu.be/iwLqufH47Ds .

Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes.

Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that functions via two multiprotein complexes, namely mTORC1 and mTORC2, each characterized by different binding partners that confer separate functions. mTORC1 function is tightly regulated by PI3-K/Akt and is sensitive to rapamycin. mTORC2 is sensitive to growth factors, not nutrients, and is associated with rapamycin-insensitivity. mTORC1 regulates protein synthesis and cell growth through downstream molecules: 4E-BP1 (also called EIF4E-BP1) and S6K. Also, mTORC2 is thought to modulate growth factor signaling by phosphorylating the C-terminal hydrophobic motif of some AGC kinases such as Akt and SGK. Recent evidence has suggested that mTORC2 may play an important role in maintenance of normal as well as cancer cells by virtue of its association with ribosomes, which may be involved in metabolic regulation of the cell. Rapamycin (sirolimus) and its analogs known as rapalogues, such as RAD001 (everolimus) and CCI-779 (temsirolimus), suppress mTOR activity through an allosteric mechanism that acts at a distance from the ATP-catalytic binding site, and are considered incomplete inhibitors. Moreover, these compounds suppress mTORC1-mediated S6K activation, thereby blocking a negative feedback loop, leading to activation of mitogenic pathways promoting cell survival and growth. Consequently, mTOR is a suitable target of therapy in cancer treatments. However, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. In recent years, new pharmacologic agents have been developed which can inhibit these complexes via ATP-binding mechanism, or dual inhibition of the canonical PI3-K/Akt/mTOR signaling pathway. These compounds include WYE-354, KU-003679, PI-103, Torin1, and Torin2, which can target both complexes or serve as a dual inhibitor for PI3-K/mTOR. This investigation describes the mechanism of action of pharmacological agents that effectively target mTORC1 and mTORC2 resulting in suppression of growth, proliferation, and migration of tumor and cancer stem cells.

Symptomatic de novo arteriovenous malformation in an adult: Case report and review of the literature.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) have been long thought to be a congenital anomaly of vasculogenesis in which arteries and veins form direct connections forming a vascular nidus without an intervening capillary bed or neural tissue. Scattered case reports have described that AVMs may form de novo suggesting they can become an acquired lesion. CASE DESCRIPTION: The current case report describes a patient who presented with new-onset seizures with an initial negative magnetic resonance imaging (MRI) of the brain and subsequently developed an AVM on a MRI 9 years later. CONCLUSION: This case joins a small, but growing body of literature that challenges the notion that all AVMs are congenital.

Hemorrhagic ganglioglioma of the posterior fossa: case report.

Gangliogliomas are rare tumors of the central nervous system that are usually found in the supratentorial compartment, although cases throughout the nervous system have been described. They are generally low-grade malignancies that are amenable to cure by surgical resection. Most manifest as seizures, though, based on location, they can present with focal neurological deficits. We present here a rare case of an infratentorial ganglioglioma presenting with hemorrhage. To our knowledge this is the only reported case of a hemorrhagic ganglioglioma and, as such, we examine its possible prognosis.