Showing papers by "Juan C. Fernandez-Miranda published in 2016"

Subcomponents and connectivity of the superior longitudinal fasciculus in the human brain

Abstract: The subcomponents of the human superior longitudinal fasciculus (SLF) are disputed. The objective of this study was to investigate the segments, connectivity and asymmetry of the SLF. We performed high angular diffusion spectrum imaging (DSI) analysis on ten healthy adults. We also conducted fiber tracking on a 30-subject DSI template (CMU-30) and 488-subject template from the Human Connectome Project (HCP-488). In addition, five normal brains obtained at autopsy were microdissected. Based on tractography and microdissection results, we show that the human SLF differs significantly from that of monkey. The fibers corresponding to SLF-I found in 6 out of 20 hemispheres proved to be part of the cingulum fiber system in all cases and confirmed on both DSI and HCP-488 template. The most common patterns of connectivity bilaterally were as follows: from angular gyrus to caudal middle frontal gyrus and dorsal precentral gyrus representing SLF-II (or dorsal SLF), and from supramarginal gyrus to ventral precentral gyrus and pars opercularis to form SLF-III (or ventral SLF). Some connectivity features were, however, clearly asymmetric. Thus, we identified a strong asymmetry of the dorsal SLF (SLF-II), where the connectivity between the supramarginal gyrus with the dorsal precentral gyrus and the caudal middle frontal gyrus was only present in the left hemisphere. Contrarily, the ventral SLF (SLF-III) showed fairly constant connectivity with pars triangularis only in the right hemisphere. The results provide a novel neuroanatomy of the SLF that may help to better understand its functional role in the human brain.

The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation.

Abstract: OBJECT The dentatorubrothalamic tract (DRTT) is the major efferent cerebellar pathway arising from the dentate nucleus (DN) and decussating to the contralateral red nucleus (RN) and thalamus. Surprisingly, hemispheric cerebellar output influences bilateral limb movements. In animals, uncrossed projections from the DN to the ipsilateral RN and thalamus may explain this phenomenon. The aim of this study was to clarify the anatomy of the dentatorubrothalamic connections in humans. METHODS The authors applied advanced deterministic fiber tractography to a template of 488 subjects from the Human Connectome Project (Q1–Q3 release, WU-Minn HCP consortium) and validated the results with microsurgical dissection of cadaveric brains prepared according to Klingler’s method. RESULTS The authors identified the “classic” decussating DRTT and a corresponding nondecussating path (the nondecussating DRTT, nd-DRTT). Within each of these 2 tracts some fibers stop at the level of the RN, forming the dentatorubro tract and th...

Human Connectome-Based Tractographic Atlas of the Brainstem Connections and Surgical Approaches.

Abstract: BACKGROUND The brainstem is one of the most challenging areas for the neurosurgeon because of the limited space between gray matter nuclei and white matter pathways. Diffusion tensor imaging-based tractography has been used to study the brainstem structure, but the angular and spatial resolution could be improved further with advanced diffusion magnetic resonance imaging (MRI). OBJECTIVE To construct a high-angular/spatial resolution, wide-population-based, comprehensive tractography atlas that presents an anatomical review of the surgical approaches to the brainstem. METHODS We applied advanced diffusion MRI fiber tractography to a population-based atlas constructed with data from a total of 488 subjects from the Human Connectome Project-488. Five formalin-fixed brains were studied for surgical landmarks. Luxol Fast Blue-stained histological sections were used to validate the results of tractography. RESULTS We acquired the tractography of the major brainstem pathways and validated them with histological analysis. The pathways included the cerebellar peduncles, corticospinal tract, corticopontine tracts, medial lemniscus, lateral lemniscus, spinothalamic tract, rubrospinal tract, central tegmental tract, medial longitudinal fasciculus, and dorsal longitudinal fasciculus. Then, the reconstructed 3-dimensional brainstem structure was sectioned at the level of classic surgical approaches, namely supracollicular, infracollicular, lateral mesencephalic, perioculomotor, peritrigeminal, anterolateral (to the medulla), and retro-olivary approaches. CONCLUSION The advanced diffusion MRI fiber tracking is a powerful tool to explore the brainstem neuroanatomy and to achieve a better understanding of surgical approaches. ABBREVIATIONS CN, cranial nerveCPT, corticopontine tractCST, corticospinal tractCTT, central tegmental tractDLF, dorsal longitudinal fasciculusHCP, Human Connectome ProjectML, medial lemniscusMLF, medial longitudinal fasciculusRST, rubrospinal tractSTT, spinothalamic tract.

Visualization of Cranial Nerves Using High-Definition Fiber Tractography.

Abstract: BACKGROUND: Recent studies have demonstrated diffusion tensor imaging tractography of cranial nerves (CNs). Spatial and angular resolution, however, is limited with this modality. A substantial improvement in image resolution can be achieved with high-angle diffusion magnetic resonance imaging and atlas-based fiber tracking to provide detailed trajectories of CNs. OBJECTIVE: To use high-definition fiber tractography to identify CNs in healthy subjects and patients with brain tumors. METHODS: Five neurologically healthy adults and 3 patients with brain tumors were scanned with diffusion spectrum imaging that allowed high-angular-resolution fiber tracking. In addition, a 488-subject diffusion magnetic resonance imaging template constructed from the Human Connectome Project data was used to conduct atlas space fiber tracking of CNs. RESULTS: The cisternal portions of most CNs were tracked and visualized in each healthy subject and in atlas fiber tracking. The entire optic radiation, medial longitudinal fasciculus, spinal trigeminal nucleus/tract, petroclival portion of the abducens nerve, and intrabrainstem portion of the facial nerve from the root exit zone to the adjacent abducens nucleus were identified. This suggested that the high-angular-resolution fiber tracking was able to distinguish the facial nerve from the vestibulocochlear nerve complex. The tractography clearly visualized CNs displaced by brain tumors. These tractography findings were confirmed intraoperatively. CONCLUSION: Using high-angular-resolution fiber tracking and atlas-based fiber tracking, we were able to identify all CNs in unprecedented detail. This implies its potential in localization of CNs during surgical planning. ABBREVIATIONS: CN, cranial nerve ABBREVIATIONS: DSI, diffusion spectrum imaging ABBREVIATIONS: DTI, diffusion tensor imaging ABBREVIATIONS: HCP, Human Connectome Project ABBREVIATIONS: HDFT, high-definition fiber tractography ABBREVIATIONS: MLF, medial longitudinal fasciculus ABBREVIATIONS: ODF, orientation distribution function ABBREVIATIONS: ROI, region of interest

Endoscopic transnasal skull base surgery: pushing the boundaries

Abstract: The endoscopic endonasal approach (EEA) has significantly evolved since its initial uses in pituitary and sinonasal surgery. The literature is filled with reports and case series demonstrating efficacy and advantages for the entire ventral skull base. With competence in 'minimally invasive' parasellar approaches, larger and more complex approaches were developed to utilize the endonasal corridor to create maximally invasive endoscopic skull base procedures. The challenges of these more complex endoscopic procedures include a long learning curve and navigating in a narrow corridor; reconstruction of defects presented new challenges and early experience revealed a significantly higher risk of cerebrospinal fluid leak. Despite these challenges, there are many benefits to the EEA including avoidance of brain and neurovascular retraction, improved visualization, a direct corridor onto many tumors and the two-surgeon approach. Most importantly, the EEA provides a midline corridor to directly access tumors, which displace critical neurovascular structures laterally, giving it an inherent advantage of minimizing any manipulation of these structures and thus decreasing their potential injury.

Endoscopic Endonasal Optic Nerve Decompression for Fibrous Dysplasia.

Abstract: Objective To evaluate visual outcomes and potential complications for optic nerve decompression using an endoscopic endonasal approach (EEA) for fibrous dysplasia. Design Retrospective chart review of patients with fibrous dysplasia causing extrinsic compression of the canalicular segment of the optic nerve that underwent an endoscopic endonasal optic nerve decompression at the University of Pittsburgh Medical Center from 2010 to 2013. Main Outcome Measures The primary outcome measure assessed was best-corrected visual acuity (BCVA) with secondary outcomes, including visual field testing, color vision, and complications associated with the intervention. Results A total of four patients and five optic nerves were decompressed via an EEA. All patients were symptomatic preoperatively and had objective findings compatible with compressive optic neuropathy: decreased visual acuity was noted preoperatively in three patients while the remaining patient demonstrated an afferent pupillary defect. BCVA improved in all patients postoperatively. No major complications were identified. Conclusion EEA for optic nerve decompression appears to be a safe and effective treatment for patients with compressive optic neuropathy secondary to fibrous dysplasia. Further studies are required to identify selection criteria for an open versus an endoscopic approach.

A description of the anatomy of the glossopharyngeal nerve as encountered in transoral surgery

Abstract: Objectives/Hypothesis To illustrate detailed anatomy of the extracranial portion of the glossopharyngeal nerve in the parapharyngeal space as encountered during transoral surgery. Study Design Prospective cadaveric dissection. All dissections were performed transorally and confirmed with transcervical dissection. Methods Eight color-injected cadaveric heads (16 sides) were dissected to demonstrate the course and anatomy of the glossopharyngeal nerve. Conventional external dissections were performed to verify our anatomic measurements. Anatomical measurements of the glossopharyngeal nerve, including segments, branches in each segment, relationship with stylopharyngeus muscle, internal carotid artery, and pharyngeal branch of Vagus were recorded and analyzed. Results The glossopharyngeal nerve was separated into three segments according to the relationship with the stylopharyngeus muscle. Total lengths of the glossopharyngeal nerve are 32.6 ± 3.1 (left side) and 30.6 ± 3.7 (right side) mm, respectively. The average number of branches in the upper, middle, and lower segments is 3 (range 1–3), 4 (range 2–4), and 3 (range 1–3), respectively. The total number of branches is 8 (range 6–9). The average diameter of the main trunk of the glossopharyngeal nerve is 1.2 ± 0.3 mm, and the average diameter of the lingual branch of the glossopharyngeal nerve is approximately 0.6 ± 0.2 mm. In 75% of cases, pharyngeal branch of Vagus crosses the glossopharyngeal nerve, whereas in 25% of cases it parallels the course of the glossopharyngeal nerve to form the pharyngeal nerve plexus to innervate the pharyngeal wall. Conclusion Understanding the precise and detailed anatomy of the glossopharyngeal nerve in the parapharyngeal space is important in transoral surgery for indications such as transoral robotic surgery or transoral laser microsurgery tumor resection, lingual tonsillectomy, glossopharyngeal neuralgia, glossopharyngeal nerve block, and internal carotid artery dissection. Level of Evidence N/A. Laryngoscope, 126:2010–2015, 2016

Visual Outcomes after Endoscopic Endonasal Approach for Craniopharyngioma: The Pittsburgh Experience

Abstract: This series of patients has been published in the neurosurgical literature earlier this year, detailing multiple aspects of both the surgical technique and postoperative outcomes. Our aim in this series is not to revisit all the aspects of this publication, but rather to analyze more specifically the benefits of this procedure as it pertains to the preservation of neurological structures of vision-specifically the optic chiasm-and provide a more detailed analysis of visual outcomes in these patients.

Total Human Eye Allotransplantation: Developing Surgical Protocols for Donor and Recipient Procedures.

Abstract: Background Vascularized composite allotransplantation of the eye is an appealing, novel method for reconstruction of the nonfunctioning eye. The authors' group has established the first orthotopic model for eye transplantation in the rat. With advancements in immunomodulation strategies together with new therapies in neuroregeneration, parallel development of human surgical protocols is vital for ensuring momentum toward eye transplantation in actual patients. Methods Cadaveric donor tissue harvest (n = 8) was performed with orbital exenteration, combined open craniotomy, and endonasal approach to ligate the ophthalmic artery with a cuff of paraclival internal carotid artery, for transection of the optic nerve at the optic chiasm and transection of cranial nerves III to VI and the superior ophthalmic vein at the cavernous sinus. Candidate recipient vessels (superficial temporal/internal maxillary/facial artery and superficial temporal/facial vein) were exposed. Vein grafts were required for all anastomoses. Donor tissue was secured in recipient orbits followed by sequential venous and arterial anastomoses and nerve coaptation. Pedicle lengths and calibers were measured. All steps were timed, photographed, video recorded, and critically analyzed after each operative session. Results The technical feasibility of cadaveric donor procurement and transplantation to cadaveric recipient was established. Mean measurements included optic nerve length (39 mm) and caliber (5 mm), donor artery length (33 mm) and caliber (3 mm), and superior ophthalmic vein length (15 mm) and caliber (0.5 mm). Recipient superficial temporal, internal maxillary artery, and facial artery calibers were 0.8, 2, and 2 mm, respectively; and superior temporal and facial vein calibers were 0.8 and 2.5 mm, respectively. Conclusion This surgical protocol serves as a benchmark for optimization of technique, large-animal model development, and ultimately potentiating the possibility of vision restoration transplantation surgery. Clinical question/level of evidence Therapeutic, V.

Endoscopic endonasal skull base surgery for vascular lesions: a systematic review of the literature.

Abstract: Introduction Endoscopic endonasal skull base surgery for vascular lesions is a controversial topic in neurosurgical practice. Concerns regarding the ability to effectively work through the relatively narrow and deep endonasal corridor and manage serious hemorrhagic complications such as inadvertent internal carotid artery (ICA) injury during endoscopic surgery (EES) are relevant sources of disagreement between neurosurgeons. Nevertheless, following careful preoperative evaluation, EES may be indicated for rare, well-selected cases, including medially-projecting paraclinoid aneurysms and cavernous malformations (CMs) located next to the ventral surface of the brainstem. To date, only small retrospective case series and case reports, attesting the safety, feasibility and technical aspects of the EES for aneurysm clipping, CM resection and arterio-venous malformations (AVMs), have been published in the literature. Evidence acquisition In this manuscript, we conducted a systematic review of the literature applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on EES for treatment of intracranial vascular lesions. We discuss the indications, advantages, limitations and technical aspects of EES for vascular lesions. Evidence synthesis and conclusions Although rarely indicated, EES may be considered as an alternative treatment and part of the armamentarium of cerebrovascular neurosurgeons dealing with these challenging lesions.

Clinical Considerations for Vascularized Composite Allotransplantation of the Eye.

Abstract: Vascularized composite allotransplantation represents a potential shift in approaches to reconstruction of complex defects resulting from congenital differences as well as trauma and other acquired pathology. Given the highly specialized function of the eye and its unique anatomical components, vascularized composite allotransplantation of the eye is an appealing method for restoration, replacement, and reconstruction of the nonfunctioning eye. Herein, we describe conventional treatments for eye restoration and their shortcomings as well as recent research and events that have brought eye transplantation closer to a potential clinical reality. In this article, we outline some potential considerations in patient selection, donor facial tissue procurement, eye tissue implantation, surgical procedure, and potential for functional outcomes.

2-Hydroxy-Glutarate 3-Dimensional Functional Spectroscopy in the Evaluation of Isocitrate Dehydrogenase-Mutant Glioma Response to Therapy.

Abstract: S omatic mutations of the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2, respectively) are found in approximately 80% of World Health Organization (WHO) grade II/III gliomas and secondary glioblastomas (WHO grade IV). These mutations result in overreduction of a-ketoglutarate to the putative oncometabolite 2-hydroxyglutarate (2HG). The accumulation of 2HG in cells is thought to play a key role in accelerating malignant transformation by promoting DNA hypermethylation, which in turn leads to genome-wide derangements in the epigenetic control of gene expression. Because IDH-mutant gliomas have been found to have a favorable overall prognosis compared with wild-type tumors, the accumulation of 2HG in tumor cells has been studied as a predictive biomarker of IDH-mutant tumors. Noninvasive detection of 2HG with magnetic resonance spectroscopy (MRS) has gone through multiple phases. Although initial studies focused on the diagnostic and prognostic values of 2HG, a more recent study suggests that this molecule could be used for early identification of response to treatment. Andronesi et al hypothesized that the decrease in 2HG levels as a result of antitumor therapy could be measureable by MRS. They performed a prospective longitudinal imaging study in 25 patients with IDH-mutant glioma receiving adjuvant radiation and chemotherapy. Using a newly developed 3-dimensional MRS imaging protocol, they were able to achieve optimal temporal stability and spatial coverage of 2HG quantification, overcoming many of the limitations related to the single-vortex or single-slice methods. More specifically, 3dimensional spectroscopy for 2HG has been shown to eliminate the sampling bias encountered in the other methods by taking into consideration the heterogeneity of the tumor. Next, Andronesi et al proposed functional spectroscopic maps as a metric to quantify spatiotemporal changes of metabolite levels. The changes in these maps were correlated to changes in the patients’ Karnofsky Performance Status during treatment. In addition, the 2HG functional spectroscopic map changes were compared against other imaging modalities for determining treatment response such as the Revised Assessment in Neuro-Oncology criteria, diffusion magnetic resonance imaging, or other spectroscopic indices. As hypothesized, even within 1 to 3 months after completion of therapy, the investigators found a significant decrease in the mean 2HG levels on posttreatment scans compared with pretreatment scans. Larger posttreatment decreases in the ratios of 2HG to creatinine were observed in lower-grade (WHO grades II/III) and smaller gliomas. Remarkably, significant changes were not observed in the same time frame in any of the other measured metabolites. This was true even for choline, a widely measured metabolite used as an index of tumor progression. The investigators therefore concluded that 2HG might actually be more sensitive to treatment effect than other metabolites in the early posttreatment period. In addition, this study established a significant correlation between the changes in 2HG levels and functional outcomes. More specifically, the fractional volume of decreased ratios of 2HG to creatinine significantly correlated with increases in the patients’ Karnofsky Performance Status. Accordingly, the investigators concluded that 2HG has the potential to serve as an objective end point to assess early response to treatment, which would be complementary to conventional clinical outcome criteria in IDH-mutant clinical trials. The findings described could also facilitate future clinical trials involving novel drugs targeting IDH-mutant gliomas (eg, selective R132H-IDH1 inhibitors and DNA demethylating agents). The study represents a valuable radiogenomic paradigm with promising future clinical applications. The small number of subjects harboring different grades of glioma, however, limits the generalizability of the conclusions. Future prospective studies recruiting more subjects with different histological types and for longer periods of time are necessary to validate these findings but also to further define the role 2HG spectroscopy as a surrogate of response to treatment.

Prof. Rhoton: Master and Mentor.

Abstract: It is with great sorrow, but profound gratitude that I write thesewords in remembrance of Prof. Albert L. Rhoton Jr. Using his own expression, not in my wildest dreams I could have imagined working closely with him, one of the greatest medical souls that have ever lived. I had the unique privilege of spending two extraordinary years in his laboratory, and here, a decade later, I would like to illustrate what it was like and what it meant to be his fellow. Prof. Rhoton established his microneuroanatomy laboratory at Mayo Clinic in the late 1960s, as he would say “not to write a paper, but to improve the life ofmy patients.” In 1974, he created his microsurgery education center at the University of Florida, with a missionary leitmotiv: “Every Second of Every Day,” he wanted to train and teach enough surgeons in microsurgical neuroanatomy and techniques so that there would be someone having surgery during every second of every day that was being made better because of his influence (►Fig. 1). After 42 years with more than 100 fellows, more than 500 scientific articles, and thousands of lectures later, there is no question he has accomplished that goal: patients all over theworldwill continue benefiting from Prof. Rhoton’s work forever. When I started training in Prof. Rhoton’s laboratory in 2005, he was a living legend, the father of microsurgical neuroanatomy, and mentor for many world-class neurosurgeons (►Fig. 2). I remember vividly the initial meeting in his office to discuss the goals for my fellowship, and there I felt for the first time his magic aura of love and kindness that would irradiate and comfort everyone around—like the giant oak that gives shadow and protects from the bright sun. “Other than working in the lab, you may want to visit Florida’s coast and Disneyworldwith your wife,” he saidwith that smile that would illuminate your soul. We had sold everything we had back in Spain to fund our stay and work in Prof. Rhoton’s laboratory looking for microsurgical training and anatomical knowledge, and we found so much more. Since then, every single second we spent with him and his family was unique and special. All fellows and families particularly enjoyed those pizza parties at Rhoton’s that Mrs. Joyce Rhoton organized to celebrate every fellow graduation (►Fig. 3). Dr. Rhoton was a devoted family man and he tremendously enjoyed being around and playing with children (►Fig. 4). Joyce, his wife for 58 years, is the great woman behind the great man. Her dedication and support, always by his side, is a key aspect of Prof. Rhoton’s successful biography (►Fig. 5). The working philosophy in the laboratory was defined by Prof. Rhoton’s description of the brain as the crown jewel of creation and his quest for beauty and perfection. I attended my first days in the laboratory observing with astonishment the exquisite dissections that the fellows were performing. I found out then that those extremely beautiful and unreal