Novel "T-Dimension" Therapies for Pediatric Optic Pathway Glioma: A Timely, Targeted, and Tailored Treatment Trend.

INTRODUCTION: Novel targeted and tailored therapies can substantially improve the prognosis for optic pathway glioma (OPG), especially when implemented in a timely manner. However, their tremendous potential remains underestimated. Therefore, in this study, we provide an updated overview of the clinical trials, current trends, and future perspectives for OPG's novel therapeutic strategies. METHODS: We completed an extensive literature review using the PubMed, MEDLINE, and ClinicalTrials.gov databases. We analyzed and reported the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Thioguanine, procarbazine, lomustine, and vincristine/vinblastine, as well as cisplatin-etoposide, provided excellent results in advanced-phase trials. Selumetinib and trametinib, two oral MEK inhibitors, have been approved for recurrent or refractory OPGs in association with the angiogenetic inhibitor bevacizumab. Among the mTOR inhibitors, everolimus and sirolimus showed the best results. Stereotactic radiosurgery and proton beam radiation therapy have advantages over conventional radiotherapy regimens. Timely treatment is imperative for acute visual symptoms with evidence of tumor progression. This latest evidence can help define a novel "T-Dimension" for pediatric OPG therapies. CONCLUSION: The novel "T-Dimension" for pediatric OPGs is based on recent evidence-based treatments, including combination chemotherapy regimens, molecular targeted therapies, stereotactic radiosurgery, and proton beam radiation therapy. Additional clinical trials are essential for validating each of these new therapies.

Shedding the Light on the Natural History of Intracranial Aneurysms: An Updated Overview.

The exact molecular pathways underlying the multifactorial natural history of intracranial aneurysms (IAs) are still largely unknown, to the point that their understanding represents an imperative challenge in neurovascular research. Wall shear stress (WSS) promotes the genesis of IAs through an endothelial dysfunction causing an inflammatory cascade, vessel remodeling, phenotypic switching of the smooth muscle cells, and myointimal hyperplasia. Aneurysm growth is supported by endothelial oxidative stress and inflammatory mediators, whereas low and high WSS determine the rupture in sidewall and endwall IAs, respectively. Angioarchitecture, age older than 60 years, female gender, hypertension, cigarette smoking, alcohol abuse, and hypercholesterolemia also contribute to growth and rupture. The improvements of aneurysm wall imaging techniques and the implementation of target therapies targeted against inflammatory cascade may contribute to significantly modify the natural history of IAs. This narrative review strives to summarize the recent advances in the comprehension of the mechanisms underlying the genesis, growth, and rupture of IAs.

Surgical management of thoracolumbar junction fractures: An evidence-based algorithm.

Background: The management of thoracolumbar junction (TLJ) fractures, involving the restoring anatomical stability and biomechanics properties, still remains a challenge for neurosurgeons.Despite the high frequency of these injuries, specific treatment guidelines, set on biomechanical properties, have not yet been assumed. The present study is meant to propose an evidence-based treatment algorithm. The primary aim for the protocol validation was the assessment of postoperative neurological recovery. The secondary objectives concerned the evaluation of residual deformity and rate of hardware failure. Technical nuances of surgical approaches and drawbacks were further discussed. Methods: Clinical and biomechanical data of patients harboring a single TLJ fracture, surgically managed between 2015 and 2020, were collected. Patients' cohorts were ranked into 4 groups according to Magerl's Type, McCormack Score, Vaccaro PLC point, Canal encroachment, and Farcy Sagittal Index. The outcome measures were the early/late Benzel-Larson Grade and postoperative kyphosis degree to estimate neurological status and residual deformity, respectively. Results: 32 patients were retrieved, 7, 9, 8, and 8 included within group 1, 2, 3, and 4, respectively. Overall neurological outcomes significantly improved for all patients at every follow-up stage (p â€‹< â€‹0.0001). Surgeries gained a complete restoration of post-traumatic kyphosis in the entire cohort (p â€‹< â€‹0.0001), except for group 4 which experienced a later worsening of residual deformity. Conclusions: The choice of the most appropriate surgical approach for TLJ fractures is dictated by morphological and biomechanical characteristics of fracture and the grade of neurological involvement. The proposed surgical management protocol was reliable and effective, although further validations are needed.

Far Lateral Approach.

The far lateral approach is an inferolateral extension of the lateral suboccipital approach. Designed for clipping of the aneurysms of the vertebrobasilar junction and proximal segments of the posterior inferior cerebellar artery, it became over the years a workhorse approach for ventral foramen magnum meningiomas and other intradural lesions located anterior to the dentate ligament.  This article summarizes the technical key aspects of the far lateral approach and transcondylar, supracondylar, and paracondylar extension.

Cranio-Orbito-Zygomatic Approach.

The cranio-orbito-zygomatic (COZ) approach consists of an extension of the pterional approach characterized by the removal of the superolateral part of the orbital rim and zygoma. This key step tremendously increases the angular exposure to some deep targets and overall surgical freedom to the lesion. In this article we review the technical variations of the COZ approach, mainly focusing on the differential quantitative effects coming from the orbital osteotomy compared to the zygomatic one.

Pterional Approach.

The pterional approach is a workhorse in neurosurgery, to the point where perfect knowledge of its execution is essential in neurosurgical daily practice. The pterional transsylvian corridor is used to treat aneurysms involving anterior circulation, basilar apex, the proximal segment of the superior cerebellar and posterior cerebral artery, arteriovenous malformations and cavernous hemangiomas of the basal forebrain, anterior and middle skull base tumors, gliomas of the frontal, parietal, and temporal opercula, insula, mediobasal temporal region, cerebral peduncles, interpeduncular fossa, and also orbital lesions. We herein overview the core technique and variations of the pterional approach aimed at broadening surgical freedom and decreasing the risk of approach-related complications.

Microsurgical Neurovascular Anatomy of the Brain: The Posterior Circulation (Part II).

Introduction Vascular complications of posterior fossa surgery are often deadly although widely preventable through in-depth knowledge of the microsurgical neurovascular anatomy of the infratentorial region and careful surgical planning.   The target of this study is to provide a synoptic overview of the normal anatomy and anatomic variants of the infratentorial neurovascular system, critical to safely operate tumors and neurovascular pathologies of the posterior fossa. Methods Two fresh-frozen and five formalin-fixed cadaveric heads were used. Cervical arteries and internal jugular veins were injected with red and blue latex, respectively. The heads were dissected under a surgical microscope, with magnifications ranging between 3× to 40×, focusing on the infratentorial region. The infratentorial arteries, their collaterals and perforating branches, the brainstem and cerebellar veins, the tentorial venous sinuses, and the relative vascular territories were summarized according to a synoptic approach.    Results The vertebral artery, basilar artery (BA), and posterior cerebral artery (PCA) are the main sources of the arterial supply of the brainstem and cerebellum through the posterior inferior cerebellar artery (PICA), the anterior inferior cerebellar artery (AICA), the superior cerebellar artery (SCA), and the perforating arteries. The perforating arteries of the vertebrobasilar system derive from the PICA, BA, AICA, SCA, and PCA, and provide for a key contribution to the vascularization of the midbrain, pons, medulla oblongata, fourth ventricle, cerebellar and cerebral peduncles, thalamus, hypothalamus, subthalamus, posterior part of the internal capsule, and optic tract. The distal segments and branches of the PCA also add a significant arterial supply to the temporal, occipital, and parietal lobes. The venous outflow of the posterior fossa is a prerogative of the internal jugular veins via the tentorial venous sinuses. Conclusion A perfect mastery of the arterial, venous, and cisternal anatomy of the infratentorial region is vital for the planning and execution of the whole range of posterior fossa approaches.

Microsurgical Neurovascular Anatomy of the Brain: The Anterior Circulation (Part I).

Introduction Treatment of cranial neurovascular pathology requires a detailed understanding of the brain, head, and neck vasculature. This study aims at a comprehensive overview of the microsurgical anatomy of the anterior cerebral circulation. Methods Five formalin-fixed adult cadaveric heads were used. Common carotid arteries, vertebral arteries, and internal jugular veins were injected with colored latex (red for arteries and blue for veins). The heads were dissected under a surgical microscope with magnifications ranging between 3× to 40× focusing on the anterior circulation. A synoptic approach was used to describe in detail the segments, branches, perforating arteries, veins, and vascular territories of the cerebral arteries and veins. Results The anterior arterial circulation of the brain is provided by the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), anterior communicating artery (ACoA), and perforating arteries. Perforating arteries of the anterior circulation arise from the ICA, ACA, MCA, ACoA, and posterior communicating artery (PCoA). The distal segments and collateral branches of the ICA, ACA, and MCA give the arterial supply to the largest part of the forebrain, whereas perforating arteries of the anterior circulation are related to the striatum, thalamus, and basal ganglia. The ACoA is the core functional anastomosis between the left and right ICA systems. The external carotid artery provides the vascular supply to the region of the face, head, and neck, and most of the meninges. The internal jugular venous system is composed of the internal and external jugular veins, which constitutes the outflow of the cerebral and facial venous system, respectively. Conclusion Thorough knowledge of the topographic, cisternal, and functional anatomy of the anterior circulation of the brain is critical for surgery of the supratentorial lesions.

The Modular Concept in Skull Base Surgery: Anatomical Basis of the Median, Paramedian and Lateral Corridors.

Introduction A thorough understanding of skull base anatomy is imperative to perform safely and effectively any skull base approach. In this article, we examine the microsurgical anatomy of the skull base by proposing a modular topographic organization in the median, paramedian, and lateral surgical corridors in relation to transcranial and endoscopic approaches. Methods Five dry skulls were studied focusing on the intracranial and exocranial skull base. Two lines were drawn parallel to the lateral border of the cribriform plate of the ethmoid bone and foramen lacerum, respectively. Lines 1 and 2 delimited the median, paramedian and lateral corridors of the skull base. The bony structures that formed each corridor were carefully reviewed in relation to the planning and execution of the skull base transcranial and endoscopic approaches. Results The midline corridor involves the crista galli, cribriform plate, planum and jugum sphenoidale, chiasmatic sulcus, tuberculum sellae, sellar region, dorsum sellae, clivus, and foramen magnum. The paramedian corridor includes the fovea ethmoidalis, the root of the lesser and greater sphenoid wing, anterior clinoid process, foramen lacerum, the upper half of the petro-occipital suture, and jugular tubercle. The lateral corridors include the orbital plates, sphenoid wings, squamosal and petrous parts of the temporal bone, caudal aspect of the petro-occipital suture, internal auditory canal, jugular foramen, the sulcus of the sigmoid sinus. Conclusion In-depth three-dimensional knowledge of skull base anatomy based on the modular concept of the surgical corridors is critical for the planning and execution of the transcranial and endoscopic approaches.