Safety and effectiveness of evicel® fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery.

PURPOSE: Cerebrospinal fluid (CSF) leakage is a challenging complication of intradural cranial surgery, and children are particularly at risk. The use of dural sealants confers protection in adults, but pediatric studies are scarce. We evaluated the safety and efficacy of Evicel® fibrin sealant as an adjunct to primary dural suturing in children undergoing cranial surgery. METHODS: A multicenter trial prospectively enrolled pediatric subjects (< 18 years) undergoing cranial neurosurgery who, upon completion of primary sutured dural repair, experienced CSF leakage. As agreed by the EMA Evicel® Pediatric Investigation Plan, 40 subjects were intra-operatively randomized 2:1 to Evicel® or additional sutures ('Sutures'). Data analysis was descriptive. The efficacy endpoint was treatment success rate, with success defined as intra-operative watertight closure after provocative Valsalva maneuver (primary endpoint). Safety endpoints were postoperative CSF leakage (incisional CSF leakage, pseudomeningocele or both) and surgical site complications (secondary endpoints). RESULTS: Forty subjects (0.6-17 years) were randomized to Evicel® (N = 25) or Sutures (N = 15) (intention-to-treat). Intracranial tumor was the most common indication and procedures were mostly supratentorial craniotomies. Success rates were 92.0% for Evicel® and 33.3% for Sutures, with a 2.76 estimated ratio of success rates (Farrington-Manning 95% CI [1.53, 6.16]). Sensitivity analyses in per-protocol and safety sets showed similar results. Despite a higher rescue treatment rate, the frequencies of postoperative CSF leakage and wound complications were higher for Sutures than for Evicel®. CONCLUSION: This small-scale prospective study shows Evicel® treatment to be safe and effective as an adjunct to primary sutured dura mater closure in a pediatric population. Compared to additional sutures, Evicel® was associated with reduced postoperative CSF leakage and surgical site complications. (Trial registration: The trial was registered as NCT02309645 and EudraCT 2013-003558-26).

Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer's disease via MFG-E8.

Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared with non-disease controls, and that proximity to amyloid-ß plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation.

A rare presentation of a bilateral intracranial parameningeal embryonal rhabdomyosarcoma mimicking vestibular schwannoma in a two-year-old child: a case report.

Intracranial parameningeal rhabdomyosarcomas are rare, aggressive, rapidly progressive paediatric malignancies that carry a poor prognosis. The authors report a case of a 2-year-old boy who initially presented with a left facial palsy, ataxia and, shortly after, bloody otorrhoea. MRI imaging was initially suggestive of a vestibular schwannoma. However, there was rapid progression of symptoms and further MRI imaging showed very rapid increase in tumour size with mass effect and development of a similar tumour on the contralateral side. A histological diagnosis of bilateral parameningeal embryonal rhabdomyosarcoma was made. Despite treatment, progression led to hydrocephalus and diffuse leptomeningeal disease, from which the patient did not survive. Few intracranial parameningeal rhabdomyosarcomas have previously been reported and these report similar presenting symptoms and rapid disease progression. However, this is the first reported case of a bilateral intracranial parameningeal embryonal rhabdomyosarcoma which, on initial presentation and imaging, appeared to mimic a vestibular schwannoma.

Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Management of traumatic atlanto-occipital dislocation in a 10-year-old with noninvasive halo immobilization: A case report.

Background: Traumatic atlanto-occipital dislocation is an unstable injury of the craniocervical junction. For pediatric patients, surgical arthrodesis of the occipitocervical junction is the recommended management. While having a high success rate for stabilization, the fusion comes with obvious morbidity of limitation in cervical spine flexion, extension, and rotation. An alternative is external immobilization with a conventional halo. Case Description: We describe the case of a 10-year-old boy who was treated successfully for traumatic AOD with a noninvasive pinless halo. Following initial brain trauma management, we immobilized the craniocervical junction with a pinless halo after reducing the atlanto-occipital dislocation. The pinless halo was kept on at all times for the next 3 months. The craniocervical junction alignment was monitored with weekly cervical spine X-rays and CT craniocervical junction on day 15th, day 30th, and day 70th. A follow-up MRI C-spine 3 months from presentation confirmed resolution of the soft-tissue injury and the pinless halo was removed. Dynamic cervical spine X-rays revealed satisfactory alignment in both flexion and extension views. The patient has been followed up for 2 years postinjury and no issues were identified. Conclusion: Noninvasive pinless halo is a potential treatment option for traumatic pediatric atlanto-occipital dislocation. This should be considered bearing in mind multiple factors including age and weight of the patient, severity of the atlanto-occipital dislocation (Grade I vs. Grade II and incomplete vs. complete), concomitant skull and scalp injury, and patient's ability to tolerate the halo. It is vital to emphasize that this necessitates close clinicoradiological monitoring.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Guideline for the management of long tunnelled external ventricular drains in chronic hydrocephalus.

This article reports on the journey of a child with an inoperable hypothalamic-origin pilocytic astrocytoma causing hydrocephalus, which was refractory to treatment with shunts, and required a new approach. With multidisciplinary support, excellent nursing care and parental education, the child's hydrocephalus was managed long term in the community with bilateral long-tunnelled external ventricular drains (LTEVDs). This article describes the patient's journey and highlights the treatment protocols that were created to achieve this feat. Despite the difficulties in initially setting up these protocols, they proved successful and thus the team managing the patient proposed that LTEVDs are a viable treatment option for children with hydrocephalus in the context of inoperable tumours to help maximise quality of life.

Custom-Made Three-Dimensional Models for Craniosynostosis.

The use of computer-aided design and computer-aided manufacturing in oral and maxillofacial surgery is an ever-growing field.The availability of 3D models, cutting guides, and customised surgical instruments gives surgeons the opportunity to modify and improve their surgical procedures.Here, we discuss the use of computer-aided design-computer-aided manufacturing to improve the management of a case of nonsyndromic metopic synostosis through the construction of: A cutting guide for the cranium, custom-made orbital protectors, a 3D model of the predicted postoperative meninges to allow off the table bone recontouring, and a template frontal bar to allow more specific recontouring of the frontal bar.

A novel management proposal for intrinsic brainstem neurenteric cysts: case report.

Neurenteric cysts (NCs) are rare congenital lesions with epithelial mucin-secreting walls. They can occur anywhere along the neural axis, and an intrinsic midbrain cyst is extraordinary. Surgical management may pose a challenge due to the location of the lesion and adhesion of the cyst wall to the surrounding brainstem. The authors describe the first case of pediatric NC that was treated successfully with intracystic interferon-α (IFN-α).A 16-month-old baby girl presented with a 2-week history of progressive croup, vomiting, and swallowing difficulty. MRI revealed a 1.8-cm cystic intrinsic lesion in the pontomedullary region. She initially underwent posterior fossa craniotomy and drainage of the cyst under intraoperative neurophysiology monitoring. Three weeks following the procedure, her symptoms recurred, and follow-up MRI demonstrated cystic recurrence. She underwent repeat aspiration of the cyst and biopsy of the cyst wall, and INF-α-2b was injected into the cystic cavity. Her symptoms improved and completely resolved after 5 months. A 9-month follow-up brain MRI study showed complete resolution of the NC. Intracystic IFN-α injection after cystic content aspiration may be a safe treatment option for the management of intrinsic brainstem NCs. Long-term clinical and radiological follow-up is recommended.

De novo distal middle cerebral artery aneurysm post-excision of intracerebral arteriovenous malformation in an 8-year old.

Cerebral arteriovenous malformations (AVMs) are frequently associated with concurrent aneurysms. These aneurysms are commonly haemodynamically related to the AVM and can be classified into extranidal or intranidal in reference to the AVM nidus. An aneurysm arising from an artery that does not angiographically contribute to the blood flow to the AVM is uncommon. A distal middle cerebral artery (dMCA) aneurysm itself is also a rare presentation, especially in paediatric population. We present a rare case of dMCA aneurysm that was noted after successful surgical management of a ruptured AVM in an 8-year-old child and its management. BACKGROUND: About 10-30% of patients with cerebral arteriovenous malformation (AVM) have an associated artery aneurysm. The majority of these aneurysms are flow-related to the malformation. These aneurysms can be classified into extranidal or intranidal in reference to the AVM nidus Rammos et al Am J Neuroradiol 37:1966-1971, [1]. An aneurysm arising from a different artery that does not angiographically contribute to the blood flow associated with the AVM is less common and would generally be regarded as unrelated to the AVM. Distal cerebral artery aneurysm itself is also a rare presentation, comprising of 1-7% of all middle cerebral artery aneurysm. In children, mycotic infection and dissection are the two most common causes for aneurysm in this location. Unlike in adults, berry aneurysms are uncommon in children. We describe a young patient who was found to have distal middle cerebral artery (dMCA) aneurysm in follow-up DSA (Digital Subtraction Angiogram) after the initial successful surgical treatment for a cerebral frontal AVM. In this particular case, endovascular repair is thought to be the best strategy to treat the aneurysm. However, there still remains a lack of consensus of the best management strategy (surgery or endovascular) in treating flow-related aneurysms in general. This is usually based on an individual case scenario and the treatment is tailored depending on various factors including the expertise of the treating team.

Surgical management of lumbar disc herniation in children and adolescents.

Lumbar disc herniation (LDH) is a rare cause of morbidity in the paediatric population that can result in disruption to education and participation in social and athletic activities. Modern minimally invasive techniques have increasingly been adopted in paediatric spine surgery. The purpose of this review was to assess characteristics of paediatric LDH, evaluate current surgical techniques and their outcomes in recent literature, and compare paediatric outcomes with adults. A literature search was carried out identifying articles published from 2008 to 2018 relating to surgical treatment of LDH in children and adolescents. Original articles were scrutinised for outcome data and complications then compared by surgical approach. Over the last decade 1094 surgical cases have been published, mostly L4/L5 (52%) and L5/S1 (41%) intervertebral discs. These were predominantly operated with microdiscectomy and minimally invasive techniques: percutaneous endoscopic and tubular approaches to discectomy. Cystic fibrosis, trauma, extensive athletic activity, facet joint asymmetries and lumbosacral transition vertebrae may be risk factors for LDH. 55% had total resolution of pain after surgery, complications are rare and unsatisfactory resolution of pain and re-operation uncommon. In the short and medium-term, overall, paediatric patients do not have worse surgical outcomes than adult patients; they may recover faster and improve more. Minimally invasive approaches for LDH in adolescents are safe and efficacious. No technique has yet demonstrated clear superiority. Delaying surgery for conservative treatment is warranted, but for how long remains unclear.

Management of cervical spine trauma in children.

PURPOSE: Paediatric cervical spine injuries are fortunately a rare entity. However, they do have the potential for devastating neurological sequelae with lifelong impact on the patient and their family. Thus, management ought to be exceptional from the initial evaluation at the scene of the injury, through to definitive management and rehabilitation. METHODS: We set out to review cervical spine injuries in children and advise on current best practice with regards to management. RESULTS: Epidemiology, initial management at the scene of injury, radiological findings and pitfalls of cervical spine trauma are outlined. Strategies for conservative and surgical management are detailed depending on the pattern of injury. The management of spinal cord injuries without radiological abnormality (SCIWORA) and cranio-cervical arterial injuries is also reviewed. CONCLUSIONS: Due to a paucity of evidence in these rare conditions, expert opinion is necessary to guide best practice management and to ensure the best chance of a good outcome for the injured child.

Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland.

OBJECTIVES: External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk. METHODS: A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR. RESULTS: A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25-12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI. CONCLUSIONS: In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types.

Comparison of Three Different Cranio-Cervical Decompression Procedures in Children with Chiari Malformation Type I: Does the Surgical Technique Matter?

BACKGROUND/AIMS: A broad spectrum of cranio-cervical decompression techniques (CCD) is employed for the treatment of Chiari malformation type I (CM1). The aim of this study was to compare the clinical and radiological outcome of 3 different CCD performed in a single paediatric centre. METHODS: A retrospective analysis of children treated between 2008 and 2014 was performed. Three different surgical techniques were offered to the patients: an extradural osseo-ligamentous bony decompression (BD), or a BD plus opening of the dura either without duroplasty (DOWD) or with watertight expansile duroplasty (DOPD). The primary clinical outcome was measured by utilizing the Chicago Chiari Outcome Scale (CCOS). RESULTS: Forty-six children underwent 51 CCD: 17 BD, 17 DOWD, and 17 DOPD. The median follow-up period was 46 months (16-98 months). Patients who underwent BD had a shorter length of hospital stay than those who underwent DPTC and DOWD. Clinical improvement, defined by the mean CCOS score, was comparable in patients receiving BD (n = 14.6) and DOPD (n = 14.5), but lower in patients with DOWD (n = 12). Post-operative complications were noted in 7 DOWD patients (41%) and 3 DOPD patients (17.6%). CONCLUSIONS: BD is a safe and effective procedure with comparable clinical and radiological outcomes to DOPD in children with CM1. The risk of post-operative complications and worse clinical outcome was noted to be higher when performing a DOWD.

Delayed diffuse cerebellar swelling after resection of medulloblastoma: case report and review of literature.

INTRODUCTION: Delayed diffuse cerebellar swelling is a rare life-threatening complication following medulloblastoma resection. PRESENTATION: We present our experience of managing a 4-year-old who developed diffuse cerebellar swelling with upward herniation 41 days after resection of a large cell anaplastic medulloblastoma. CONCLUSION: Emergency chemotherapy alone was sufficient in promoting regression of swelling and recovery from coma. Reports of similar cases are scant. Chemotherapy may be a critical component of treatment.

Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report.

The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long-term, long-tunnelled external ventricular drain as a viable treatment option for such patients.

Focused ultrasound as a non-invasive intervention for neurological disease: a review.

Focused ultrasound (FUS) is an incision-less intervention that is a Food and Drug Association (FDA) approved surgical treatment for various pathologies including uterine fibroids and bone metastases. Recent advances in magnetic resonance imaging thermometry and ability to use FUS across the intact calvarium have re-opened interest in the use of FUS in the treatment of neurological diseases. FUS currently has a European CE mark for use in movement disorders. However, it shows potential in the treatment of other neuropathologies including tumours and as a lesional tool in epilepsy. FUS may exert its therapeutic effect through thermal or mechanical fragmentation of intracranial lesions, or by enhancing delivery of pharmaceutical agents across the blood-brain barrier. In this review, we summarise the mechanisms, clinical applications and potential future of FUS for the treatment of neurological disease. We have searched for and described the recently completed and on-going clinical trials investigating FUS for the treatment of neurological disorders. We identified phase one trials investigating utility of FUS in: movement disorders (including essential tremor and Parkinson's disease), chronic pain, obsessive-compulsive disorder and cerebral tumours. Current literature also reports pre-clinical work exploring utility in epilepsy, neurodegenerative conditions (such as Alzheimer's disease) and thrombolysis. Safety and early efficacy data are now emerging, suggesting that transcalvarial FUS is a feasible and safe intervention. Further evidence is required to determine whether FUS is an effective alternative in comparison to current neurosurgical interventions. The cost of requisite hardware is currently a barrier to widespread uptake in UK neurosurgical centres.

Application of diffusion tensor imaging and tractography of the optic radiation in anterior temporal lobe resection for epilepsy: a systematic review.

BACKGROUND: Approximately 50-100% of patients with temporal lobe epilepsy undergoing anterior temporal lobe resection (ATLR) will suffer a postoperative visual field defect (VFD) due to disruption of the optic radiation (OpR). OBJECTIVE: We conducted a systematic review of the literature to examine the role of DTI and tractography in ATLR and its potential in reducing the incidence of postoperative VFD. METHODS: We conducted an electronic literature search using PubMed, Embase, Web of Science and BMJ case report databases. Eligibility for study inclusion was determined on abstract screening using the following criteria: the study must have been (1) an original investigation or case report in humans; (2) investigating the OpR with DTI in cases of ATLR in temporal lobe epilepsy; (3) investigating postoperative VFD. All forms of ATLR and ways of assessing VFD were included to reflect clinical practice. RESULTS: 13 studies (four case reports, eight prospective observational studies, one prospective comparative trial) were included in the review, 179 (mean±SD, 13.8±12.6; range, 1-48) subjects were investigated using DTI. The time of postoperative VFD measurement differed between the detected studies, ranging from two weeks to nine years following ATLR. A modest number of studies and insufficient statistical homogeneity precluded meta-analysis. However, DTI methods were consistently accurate at quantifying and predicting postoperative damage to the OpR. These methods revealed a correlation between the extent of OpR damage and the severity of postoperative VFD. The first and only trial with 15 subjects compared to 23 controls reported that using intraoperative tractography in ATLR significantly reduces the occurrence of postoperative VFD on comparison to conventional surgical planning. CONCLUSIONS: DTI shows potential to be an effective method used in planning ATLR. Findings from a single modest sized study suggest that tractography may be employed as part of intraoperative navigation techniques in order to avoid injury to the OpR. Further research needs to be conducted to ensure the applicability and effectiveness of this technology before implementation in routine clinical practice.

Endoscopic endonasal transsphenoidal "above and below" approach to the retroinfundibular area and interpeduncular cistern--cadaveric study and case illustrations.

OBJECTIVE: To evaluate the feasibility of reaching the interpeduncular cistern (IC) through an endoscopic endonasal approach that leaves the pituitary gland in place. METHODS: In a series of 10 injected cadaver heads, the transtuberculum ("above") and transclival ("below") approaches were combined, without pituitary transposition. Using 0-degree, 30-degree, and 45-degree endoscopes, the extent of overlap and if a blind spot occurred were determined. Also, the visualization of the IC was compared with the transposition of the pituitary gland approach. Nonparametric statistics were used to evaluate the results. The approach was implemented in 2 patients. RESULTS: For both the "above" and "below" views, there was a statistically significant increase in field of view when comparing the 0-degree endoscope with either the 30-degree endoscope (P < 0.05) or the 45-degree endoscope (P < 0.05). There was no difference between the 30-degree endoscope and the 45-degree endoscope (P > 0.05) in the "below" approach, but there was a difference (P < 0.05) in the "above" approach. There was no blind spot with any combination of endoscopes. There was no practical statistically significant difference between the transposition approach and the "above and below" approach. The "above and below" approach was used successfully in 2 surgeries. CONCLUSIONS: It is possible to work both "above" and "below" the pituitary gland to reach the IC through an endoscopic endonasal approach. The advantages are the maintenance of normal pituitary and parasellar anatomy and the minimization of the size of the skull base defect. There is no blind spot using this approach that would be revealed with a pituitary transposition. The feasibility of this approach has been confirmed in 2 patients.