Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Anatomical Step-by-Step Dissection of Midline Suboccipital Approaches to the Fourth Ventricle for Trainees: Surgical Anatomy of the Telovelar, Transvermian, and Superior Transvelar Routes, Surgical Principles, and Illustrative Cases.

Introduction Safe, effective access to the fourth ventricle for oncologic resection remains challenging given the depth of location, restricted posterior fossa boundaries, and surrounding eloquent neuroanatomy. Despite description in the literature, a practical step-by step dissection guide of the suboccipital approaches to the fourth ventricle targeted to all training levels is lacking. Methods Two formalin-fixed, latex-injected specimens were dissected under microscopic magnification and endoscopic visualization. Dissections of the telovelar, transvermian, and supracerebellar infratentorial-superior transvelar approaches were performed by one neurosurgery resident (D.D.D.), under guidance of senior authors. The dissections were supplemented with representative clinical cases to highlight pertinent surgical principles. Results The telovelar and transvermian corridors afford excellent access to the caudal two-thirds of the fourth ventricle with the former approach offering expanded access to the lateral recess, foramen of Luschka, adjacent skull base, and cerebellopontine angle. The supracerebellar infratentorial-superior transvelar approach reaches the rostral third of the fourth ventricle, the cerebral aqueduct, and dorsal mesencephalon. Key steps described include positioning and skin incision, myofascial dissection, burr hole and craniotomy, durotomy, the aforementioned transventricular routes, and identification of relevant skull base landmarks. Conclusion The midline suboccipital craniotomy represents a foundational cranial approach, particularly for lesions involving the fourth ventricle. Operatively oriented resources that combine stepwise neuroanatomic dissections with representative cases provide a crucial foundation for neurosurgical training. We present a comprehensive guide for trainees in the surgical anatomy laboratory to optimize familiarity with fourth ventricle approaches, mastery of relevant microsurgical anatomy, and simultaneous preparation for learning in the operating room.

Analysis of demographics and the impact of adjuvant radiotherapy on a nationwide cohort of patients with high-grade spinal meningiomas.

Background: Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. Methods: The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan-Meier survival analysis was conducted to study overall survival. All analyses were performed on R. Results: A total of 13 184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44-68] versus 65 years [54-75]; P < .001) and were more commonly males (33% vs 20%; P < .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). Conclusions: This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.

The "candy wrapper" of the pituitary gland: a road map to the parasellar ligaments and the medial wall of the cavernous sinus.

PURPOSE: The anatomy of the medial wall of the cavernous sinus (MWCS) and parasellar ligaments (PLs) has acquired increasing importance in endoscopic endonasal (EE) surgery of the cavernous sinus (CS), including resection of the MWCS in functioning pituitary adenomas (FPAs). Although anatomical studies have been published, it represents a debated topic due to their complex morphology. The aim is to offer a description of the PLs that originate from the MWCS and reach the lateral wall of the cavernous sinus (LWCS), proposing the "candy wrapper" model. The relationships between the neurovascular structures and histomorphological aspects were investigated. METHODS: Forty-two CSs from twenty-one human heads were studied. Eleven specimens were used for EE dissection; five underwent a microscopic dissection. Five specimens were used for histomorphological analysis. RESULTS: Two groups of PLs with a fan-shaped appearance were encountered. The anterior group included the periosteal ligament (55% sides) and the carotico-clinoid complex (100% sides), formed by the anterior horizontal and the carotico-clinoid ligaments. The posterior group was formed by the posterior horizontal (78% sides), and the inferior hypophyseal ligament (34% sides). The periosteal ligament originated inferiorly from the MWCS, reaching the periosteal dura. The anterior horizontal ligament was divided in a superior and inferior branch. The superior one continued as the carotid-oculomotor membrane, and the inferior branch reached the CN VI. The carotico-clinoid ligament between the middle and anterior clinoid was ossified in 3 sides. The posterior horizontal ligament was related to the posterior genu and ended at the LWCS. The inferior hypophyseal ligament followed the homonym artery. The ligaments related to the ICA form part of the adventitia. CONCLUSION: The "candy wrapper" model adds further details to the previous descriptions of the PLs. Understanding this complex anatomy is essential for safe CS surgery, including MWCS resection for FPAs.

Anatomical step-by-step dissection of common approaches to the third ventricle for trainees: surgical anatomy of the anterior transcortical and interhemispheric transcallosal approaches, surgical principles, and illustrative pediatric cases.

PURPOSE: To create a high-quality, cadaver-based, operatively oriented resource documenting the anterior transcortical and interhemispheric transcallosal approaches as corridors to the third ventricle targeted towards neurosurgical trainees at all levels. METHODS: Two formalin-fixed, latex-injected specimens were dissected under microscopic magnification and endoscopic-assisted visualization. Dissections of the transcortical and transcallosal craniotomies with transforaminal, transchoroidal, and interforniceal transventricular approaches were performed. The dissections were documented in a stepwise fashion using three-dimensional photographic image acquisition techniques and supplemented with representative cases to highlight pertinent surgical principles. RESULTS: The anterior transcortical and interhemispheric corridors afford excellent access to the anterior two-thirds of the third ventricle with varying risks associated with frontal lobe versus corpus callosum disruption, respectively. The transcortical approach offers a more direct, oblique view of the ipsilateral lateral ventricle, whereas the transcallosal approach readily establishes biventricular access through a paramedian corridor. Once inside the lateral ventricle, intraventricular angled endoscopy further enhances access to the extreme poles of the third ventricle from either open transcranial approach. Subsequent selection of either the transforaminal, transchoroidal, or interforniceal routes can be performed through either craniotomy and is ultimately dependent on individual deep venous anatomy, the epicenter of ventricular pathology, and the concomitant presence of hydrocephalus or embryologic cava. Key steps described include positioning and skin incision; scalp dissection; craniotomy flap elevation; durotomy; transcortical versus interhemispheric dissection with callosotomy; the aforementioned transventricular routes; and their relevant intraventricular landmarks. CONCLUSIONS: Approaches to the ventricular system for maximal safe resection of pediatric brain tumors are challenging to master yet represent foundational cranial surgical techniques. We present a comprehensive operatively oriented guide for neurosurgery residents that combines stepwise open and endoscopic cadaveric dissections with representative case studies to optimize familiarity with third ventricle approaches, mastery of relevant microsurgical anatomy, and preparation for operating room participation.

Flow diversion using the Pipeline embolization device for intracranial and extracranial pseudoaneurysms: a systematic review and meta-analysis of the literature.

OBJECTIVE: Pseudoaneurysms (PSAs) are complex vascular lesions. Flow diversion has been proposed as an alternative treatment to parent artery occlusion that preserves laminar flow. The authors of the present study investigated the safety and short-term (< 1 year) and long-term (≥ 1 year) aneurysm occlusion rates following the treatment of intracranial and extracranial PSAs using the Pipeline embolization device (PED). METHODS: An electronic database search for full-text English-language articles in Ovid MEDLINE and Epub Ahead of Print, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus was conducted following the PRISMA guidelines. Studies of any design including at least 4 patients with intracranial or extracranial PSAs treated using a PED were included in this analysis. The primary outcome of interest was the rate of peri- and postprocedural complications. Secondarily, the authors analyzed the incidence of complete aneurysm occlusion. RESULTS: A total of 90 patients with 96 PSAs across 9 studies were included. The mean age was 38.2 (SD 15.14) years, and 37.8% of the patients were women. The mean PSA size was 4.9 mm. Most PSAs were unruptured, and the most common etiology was trauma (n = 32, 35.5%), followed by spontaneous formation (n = 21, 23.3%) and iatrogenic injury (n = 19, 21.1%). Among the 51 (53.1%) intracranial and 45 (46.9%) extracranial PSAs were 19 (19.8%) dissecting PSAs. Sixty-six (77.6%) PSAs were in the internal carotid artery and 10 (11.8%) in the vertebral artery. Thirty-three (34.4%) PSAs were treated with ≥ 2 devices, and 8 (8.3%) underwent adjunctive coiling. The mean clinical and angiographic follow-up durations were 10.7 and 12.9 months, respectively. The short-term (< 1 year) and long-term (≥ 1 year) complete occlusion rates were 79% (95% CI 66%-88%, p = 0.82) and 84% (95% CI 70%-92%, p = 0.95), respectively. Complication rates were 8% for iatrogenic dissection (95% CI 3%-16%, p = 0.94), 10% for silent thromboembolism (95% CI 5%-21%, p = 0.77), and 12% for symptomatic thromboembolism (95% CI 6%-23%, p = 0.48). No treatment-related hemorrhage was observed. The overall mortality rate at the last follow-up was 14%. CONCLUSIONS: The complete occlusion rate for PSAs treated with the PED was high and increased over time. Although postprocedural complications and mortality were not insignificant, flow diversion represents a reasonably safe option for managing these complex lesions.

Surgical Anatomy and Approaches of the Anterior Cranial Fossa from a Transcranial and Endonasal Perspective.

The anterior cranial fossa (ACF) is a complex anatomical region that can be affected by a broad spectrum of pathology. For the surgical treatment of these lesions, many approaches have been described, each of them with different scope and potential surgical complications, often associated with significant morbidity. Traditionally, tumors involving the ACF have been operated by transcranial approaches; however, in the last two decades, endoscopic endonasal approaches (EEAs) have been gaining popularity. In this work, the authors review and describe the anatomical aspects of the ACF and the technical nuances of transcranial and endoscopic approaches for tumors located in this region. Four approaches were performed in embalmed cadaveric specimens and the key steps were documented. Four illustrative cases of ACF tumors were selected to demonstrate the clinical application of anatomical and technical knowledge, which are essential in the preoperative decision-making process.

A review of vascular endothelial growth factor and its potential to improve functional outcomes following spinal cord injury.

Spinal cord injuries (SCI) are traumatic events with limited treatment options. Following injury, the lesion site experiences a drastic change to both its structure and vasculature which reduces its ability for tissue regeneration. Despite the lack of clinical options, researchers are investigating therapies to induce neuronal regeneration. Cell-based therapies have long been assessed in the context of SCI to promote neuronal protection and repair. Vascular endothelial growth factor (VEGF) not only demonstrates this ability, but also demonstrates angiogenic potential to promote blood vessel formation. While there have been numerous animal studies investigating VEGF, further research is still warranted to pinpoint its role following SCI. This review aims to discuss the literature surrounding the role of VEGF following SCI and its potential in promoting functional recovery.

Endoscopic endonasal surgical anatomy of the optic canal: key anatomical relationships between the optic nerve and ophthalmic artery.

PURPOSE: A detailed understanding of the neurovascular relationships between the optic nerve (ON) and the ophthalmic artery (OA) in the optic canal (OC) is paramount for safe surgery. We focused on the neurovascular anatomy of this area from both an endoscopic endonasal and transcranial trajectories to compare the surgical exposures and perspectives offered by these different views and provide recommendations to increase the intraoperative safety. METHODS: Twenty sides of ten formalin-fixed, latex-injected head specimens were utilized. The surgical anatomy and anatomical relationships of the OA in relationship to the ON along their intracranial and intracanalicular segments was studied from endoscopic endonasal and transcranial perspectives. RESULTS: Three types of OA-ON relationships at the origin of the OA were identified: inferomedial (type 1, 35%), inferior (type 2, 55%), and inferolateral (type 3, 10%). The endoscopic endonasal trajectory offers an inferomedial perspective of the ON-OA neurovascular complex, in which the OA, especially when located inferomedially, is first encountered. When comparing with the transcranial view, all OA were covered by the nerve, type 1 was located below the medial third, type 2 below the middle third, and type 3 below the lateral third of the OC. The mean extension of the intracanalicular portion of both OA and ON was 8.9 mm, while the intracranial portion of the OA and ON were 9.3 mm and 12.4 mm, respectively. The OA, endoscopically, is located within the inferior half of the OC, and occupies 39%, 43%, and 42% of the OC height at its origin, mid, and end points, respectively. The mean distance between the superior margin of the OC at its origin and superior margin of the OA is 1.4 mm. CONCLUSIONS: Detailed anatomical understanding of the OC, and the ON and OA at their intracranial and intracanalicular segments is paramount to safe surgery. When opening the OC dura endoscopically, our results suggest that a medial incision along the superior third of the OC with a proximal to distal direction is recommended to avoid injury of the OA.

Principles and strategies for step-by-step AVM excision.

Arteriovenous malformations (AVMs) are some of the most challenging surgical entities. Like any challenging surgical procedure, AVM surgery is a series of basic but fundamental steps, each with its own nuances. Despite a myriad of published material regarding AVMs, there are few succinct illustrated summaries of these steps with an accompanying elucidation of the most common pitfalls. This paper provides a step-by-step description and illustration of the basic surgical principles of AVM microsurgical resection, focusing on the main key points and addressing the critical issues that surround this surgery. Deep anatomical knowledge and presurgical planning of these basic steps, combined with good contingency management skills, are paramount for an effective and safe AVM surgery.

The endonasal midline inferior intercavernous approach to the cavernous sinus: technical note, cadaveric step-by-step illustration, and case presentation.

PURPOSE: Traditional endoscopic endonasal approaches to the cavernous sinus (CS) open the anterior CS wall just medial to the internal carotid artery (ICA), posing risk of vascular injury. This work describes a potentially safer midline sellar entry point for accessing the CS utilizing its connection with the inferior intercavernous sinus (IICS) when anatomically present. METHODS: The technique for the midline intercavernous dural access is described and depicted with cadaveric dissections and a clinical case. RESULTS: An endoscopic endonasal approach exposed the periosteal dural layer of anterior sella and CS. The IICS was opened sharply in midline through its periosteal layer. The feather knife was inserted and advanced laterally within the IICS toward the anterior CS wall, thereby gradually incising the periosteal layer of the IICS. The knife was turned superiorly then inferiorly in a vertical direction to open the anterior CS wall. This provided excellent access to the CS compartments, maintained the meningeal layer of the IICS and the medial CS wall, and avoided an initial dural incision immediately adjacent to the ICA. CONCLUSION: The midline intercavernous dural access to the CS assisted by a 90° dissector-blade is an effective modification to previously described techniques, with potentially lower risk to the ICA.

Rate of C8 Radiculopathy in Patients Undergoing Cervicothoracic Osteotomy: A Systematic Appraisal of the Literature.

BACKGROUND: The emergence of C8 radiculopathy is a known complication following cervicothoracic osteotomies. However, the clinical profile of C8 radiculopathy is not well understood. The aim of this study was to investigate the rate of C8 radiculopathy after cervicothoracic osteotomies and to form a clinical profile describing the characteristics through a systematic review of the literature. METHODS: An electronic database search for full-text English articles was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search yielded results on indications for cervicothoracic osteotomies, surgical approaches, mean follow-up time, and significant complications, including C8 radiculopathy. RESULTS: Our literature search yielded 2135 articles, of which 12 qualified to be included in the analysis. The 12 articles comprised 451 patients undergoing various osteotomy approaches. The mean age of subjects was 51.0 years (range, 11.4-63.2 years), and the majority of patients were male (66%, n = 298). Ankylosing spondylitis was the most frequent indication for surgery (44.8%, n = 202). The number of patients with postoperative C8 radiculopathy was found to decrease over time (1997-2020) by showing statistical significance (r = -0.65, P = 0.021). CONCLUSIONS: Of the 451 patients included in this study, 53 had C8 radiculopathy (11.8% of the total patient population). Moreover, the rate of C8 radiculopathy decreased over time in a statistically significant manner. An understanding of the factors associated with the incidence of C8 radiculopathy is essential for future improvement of patient outcomes.

The Posterior Septal Nasal Floor Mucosal Flap for Cranial Base Reconstruction.

OBJECTIVE: While pedicled intranasal flaps, such as the nasoseptal flap (NSF), successfully reduce postoperative CSF leaks following endoscopic endonasal approaches (EEA) to the skull base, morbidity remains prevalent. This study describes the first cadaveric description and radiographic analysis of the posterior septal nasal floor mucosal flap (PSNF) designed to reduce pedicled nasal flap morbidity. A case series is also detailed. STUDY DESIGN: Cadaveric dissection, radiographic analysis, and case series. METHODS: Seven cadaver specimens underwent harvest of the PSNF. PSNF flap dimensions were measured on the thirty deidentified sinus computed tomography (CT) scans. A retrospective case series was performed on the first set of patients who received the PSNF for reconstruction of a sellar base defect. Information concerning complications, symptoms, and the appearance of the flap was recorded from records of the patient's postoperative inpatient stay, 1-week postop visit, and 1-month postop visit. RESULTS: Cadaver dissection of the PSNF flap demonstrated good arc rotation along its pedicle with ability to cover both sellar and planum defects. Cadaveric flap measurements and CT-derived measurements estimated a mean surface area of 16.7 and 18.3 cm2 , respectively. 15 patients underwent reconstruction of a sellar or planum defect using the PSNF technique. Only one CSF leak was encountered postoperatively. Minimal crusting of the flap and donor site was seen 1 month postoperatively. CONCLUSION: The PSNF flap provides a sizeable pedicled region for reconstruction comparable to other pedicled nasal flaps. Our case series demonstrated good postoperative outcomes without reduced donor site morbidity. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1561-1568, 2022.