How I do it? Surgical clipping of a large right internal carotid artery-superior hypophyseal artery aneurysm.

BACKGROUND: Microsurgery alone often proves to be challenging in treating paraclinoid internal carotid artery (ICA) aneurysms, which are known for their complex anatomy. METHOD: A 53-year-old female with a large right ICA-superior hypophyseal artery (SHA) aneurysm underwent clipping repair. Mixed reality technology was utilized in the preoperative planning and anatomical study. During the surgery, the anterior clinoid process was removed intradurally to improve access to the aneurysm neck. The aneurysm was then secured with a long curved clip. The patient's recovery was successful without any complications. CONCLUSION: This report aims to shed light on the intricacies involved in clipping ICA-SHA aneurysms.

Analysis of relationship between superior hypophyseal artery visualization and preservation and postoperative visual field deficit in paraclinoid aneurysm.

Direct surgery for paraclinoid aneurysms can result in visual field deficit owing to compromised blood flow to the superior hypophyseal artery (SHA). However, it is rarely visualized in angiography, and discussions regarding its preservation in the field of neuro-endovascular treatment are limited. Biplane angiographic suite with high spatial resolution has been used at our institution since 2014. Since then, there were a few cases where SHAs could be visualized via digital subtraction angiography. We retrospectively analyzed the relationship between the presences and abscence of SHAs in paraclinoid aneurysms and post-procedural visual field deficit. Sixty-three paraclinoid aneuryms treated by neuro-endovascular procedure in 2014-2018 at our neurosurgery department were analyzed. Pre- and post-procedural multiplanar reconstruction imagings of three-dimensional rotation angiography were analyzed to retrospectively investigate the SHAs. SHAs were visualized in 26 patients (41%) and the median number of pre-procedurally visualized SHAs was 0 (interquartile range 0-1). Their origins were the aneurysmal necks in 11 patients (42%). In two of the 11 cases, they were noticed before coil embolization and were able to be preserved after the procedure. In the remaining nine cases, they were not pre-procedurally detected, and coiling was normally conducted. Visual field deficit occurred in one of these nine cases, but symptoms were transient, and the patient fully recovered. Because SHAs could be visualized in >40% cases and no visual field defects occurred in cases that SHAs could be identified and preserved preoperatively, we recommend their preservation during coil embolization for paraclinoid aneurysms.

Arterial Supply to the Pituitary Gland: A Comprehensive Review.

Knowledge of the blood supply to the pituitary gland is important for clinicians and surgeons. Therefore, a good working knowledge of this anatomy is important. The goal of this article was to review current anatomic knowledge of the blood supply to the pituitary gland and its clinical relevance.

The inferior intercavernous sinus: An anatomical study with application to trans-sphenoidal approaches to the pituitary gland.

OBJECTIVES: The inferior intercavernous sinus is located below the pituitary gland in the sella turcica. Its presence has been controversial among anatomists because it is not always found on radiological imaging or during cadaveric dissections; however, it is becoming a better-known structure in the neurosurgical and radiological fields, specifically with respect to transsphenoidal surgery. Therefore, the present study was performed to better elucidate this structure at the skull base. PATIENTS AND METHODS: Fifty adult, latex injected cadavers underwent dissection. The presence or absence of the inferior cavernous sinus was evaluated and when present, measurements of its width and length were made. Its connections with other intradural venous sinuses were also documented. RESULTS: An inferior intercavernous sinus was identified in 26 % of specimens. In all specimens, it communicated with the left and right cavernous sinus. The average width and length were 3 mm and 9.5 mm, respectively. In the sagittal plane, the inferior intercavernous sinus was positioned anteriorly in 31 %, at the nadir of the sella turcica in 38 %, and slightly posterior to the nadir of the sella turcica in 31 %. In two specimens (15.4 %), the sinus was plexiform in its shape. In one specimen a diploic vein connected the basilar venous plexus to the inferior intercavernous sinus on its deep surface. CONCLUSION: An improved understanding of the variable anatomy of the inferior intercavernous sinus is important in pathological, surgical, and radiological cases.

Assessment of microvessel perfusion of pituitary adenomas: a feasibility study using turbo spin-echo-based intravoxel incoherent motion imaging.

OBJECTIVES: To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo spin-echo-based diffusion-weighted imaging (SS-TSE-DWI). METHODS: We examined 51 consecutive patients with pituitary adenomas (35 non-functioning and 16 functioning) and 32 patients with normal pituitary glands using SS-TSE-DWI IVIM. The diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*) were calculated pixel-by-pixel for each adenoma and normal pituitary gland. We also obtained the pathological microvessel area (MVA) of each adenoma. The IVIM parameters in adenomas were compared with those in normal pituitary glands using the Mann-Whitney U test. The correlation between the MVA and IVIM f of adenomas was analyzed using Spearman's rank correlation coefficient. RESULTS: The mean D (× 10-3 mm2/s) in adenomas was 0.723 ± 0.253, which was significantly lower than that in normal pituitary glands (0.862 ± 0.128; p < 0.0001). The mean f (%) in adenomas was 10.74 ± 4.51, which was significantly lower than that in normal pituitary glands (13.26 ± 4.32, p = 0.0251). No significant difference was found in the mean D*. We found a significant positive correlation between MVA and f in non-functioning adenomas (ρ = 0.634, p < 0.0001) as well as in all adenomas (ρ = 0.451, p = 0.0009). CONCLUSIONS: Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-DWI IVIM is feasible. Compared to normal pituitary glands, pituitary adenomas were characterized by lower D and f. KEY POINTS: • Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-IVIM is feasible. • SS-TSE-IVIM helps with evaluation of the vascularity of pituitary lesions. • Pituitary adenomas were characterized by lower D and f than normal pituitary glands.

Labeling of Blood Vessels in the Teleost Brain and Pituitary Using Cardiac Perfusion with a DiI-fixative.

Blood vessels innervate all tissues in vertebrates, enabling their survival by providing the necessary nutrients, oxygen, and hormonal signals. It is one of the first organs to start functioning during development. Mechanisms of blood vessel formation have become a subject of high scientific and clinical interest. In adults however, it is difficult to visualize the vasculature in most living animals due to their localization deep within other tissues. Nevertheless, visualization of blood vessels remains important for several studies such as endocrinology and neurobiology. While several transgenic lines have been developed in zebrafish, with blood vessels directly visualized through expression of fluorescent proteins, no such tools exist for other teleost species. Using medaka (Oryzias latipes) as a model, the current protocol presents a quick and direct technique to label blood vessels in brain and pituitary by perfusing through the heart with fixative containing DiI. This protocol allows improvement of our understanding on how brain and pituitary cells interact with blood vasculature in whole tissue or thick tissue slices.

Imaging and Manipulating Pituitary Function in the Awake Mouse.

Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. These methodologies are now readily applicable for longitudinal studies of short-lived events (e.g., calcium signals controlling hormone exocytosis) and slowly evolving processes such as tissue remodeling in health and disease over a period of days to weeks.

The approach angle to the interoptic triangle limits surgical workspace when targeting the contralateral internal carotid artery.

BACKGROUND: The interoptic triangle (IOT) offers a key access to the contralateral carotid artery's ophthalmic segment (oICA) and its perforating branches (PB), the ophthalmic artery (OA), and the superior hypophyseal artery (SHA). It has been previously reported that the assessment of IOT's size is relevant when attempting approaches to the contralateral oICA. However, previous studies have overseen that, since the oICA is a paramedian structure and a lateralized contralateral approach trajectory is then required, the real access to the oICA is further limited by the approach angle adopted by the surgeon with respect to the IOT's plane. For this reason, we determined the surgical accessibility to the contralateral oICA and its branches though the IOT by characterizing the morphometry of this triangle relative to the optimal contralateral approach angle. METHODS: We defined the "relative interoptic triangle" (rIOT) as the two-dimensional projection of the IOT to the surgeon's view, when the microscope has been positioned with a certain angle with respect to the midline to allow the maximal contralateral oICA visualization. We correlated the surface of the rIOT to the visualization of oICA, OA, SHA, and PBs on 8 cadavers and 10 clinical datasets, using for the last a 3D-virtual reality system. RESULTS: A larger rIOT correlated positively with the exposure of the contralateral oICA (R = 0.967, p < 0.001), OA (R = 0.92, p < 0.001), SHA (R = 0.917, p < 0.001), and the number of perforant vessels of the oICA visible (R = 0.862, p < 0.001). The exposed length of oICA, OA, SHA, and number PB observed increased as rIOT's surface enlarged. The correlation patterns observed by virtual 3D-planning matched the anatomical findings closely. CONCLUSIONS: The exposure of contralateral oICA, OA, SHA, and PB directly correlates to rIOT's surface. Therefore, preoperative assessment of rIOT's surface is helpful when considering contralateral approaches to the oICA. A virtual 3D planning tool greatly facilitates this assessment.

The Superior Hypophyseal Arteries: Anatomical Study with an Endoscopic Endonasal Perspective.

BACKGROUND: The use of high-definition endoscopes in extended transsphenoidal approaches to the suprasellar area has significantly improved visualization of its vascularization. OBJECTIVE: To systematically examine the superior hypophyseal arteries (SHAs) anatomy from an endonasal endoscopic perspective. METHODS: The endoscopic endonasal transsphenoidal trans-tuberculum approach was performed in 19 adult, fresh and latex injected specimens. Dissections recordings were reviewed to analyze SHAs type, number, and branches, as well as internal carotid arteries (ICA) branches that vascularized optic nerves and chiasm. RESULTS: Identification of SHAs was possible in all specimens (37/38 sides). The number of SHAs varied from 1 to 3 per side (mean: 1.7). The anterior superior hypophyseal artery was visible in almost all cases (35/37 sides) and originated at the level of the carotid cave in 18/35 specimens; number of branches ranged from 1 to 6 (mean: 3.5), directed to the optic nerve (86%), chiasm (57%), infundibulum (86%), and/or parallel to the pituitary stalk (74%). The 4 main branches and patterns, originally described by McConnell in 1953, were confirmed. The posterior superior hypophyseal artery was evident in 28/37 sides with number of branches ranging from 0 to 4 (mean: 2.1), directed to the optic chiasm (50%), optic tract (32%), infundibulum (79%), and/or pituitary stalk (36%). The surgical implications of this study, together with anatomical and clinical videos, are also briefly discussed. CONCLUSION: SHAs constitute a complex of anterior and posterior branches that stem from the medial ICA with different patterns, vascularizing the optic apparatus and pituitary stalk.

Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary prolactinoma in rats.

Prolactinomas are the most common tumor of the human pituitary. They result in excessive prolactin secretion and important changes in the vasculature. Pericytes are perivascular cells associated with capillaries and have crucial roles in physiological and pathological neovascularization. We previously reported that pericytes produce type I and III collagens in the anterior pituitary of adult rats. In addition, pituitary pericytes contained well-developed cell organelles and actively synthesized collagens during early postnatal development. However, the characteristics of pericytes in pituitary tumors are unclear. In this study, we used diethylstilbestrol (DES)-treated rats as an animal model of prolactinoma. Using five common pericyte markers, more pericytes were observed in rats treated with DES for 3 months (prolactinoma) compared to the control. Transmission electron microscopy revealed that attached and semidetached pericytes exhibited active cell organelles. Moreover, we identified pericyte migration between capillaries. Although the fine structure of pituitary pericytes was active in prolactinoma, expressions of type I and III collagen mRNAs were greatly diminished. In sum, the characteristics and functions of pericytes were altered in pituitary tumors. This study is the first to clarify fine structural changes of pericytes in rat prolactinomas and improves our understanding of the function of pericytes under pathological conditions.

Hypoxia Inducible Factor Expression and Angiogenesis - Analysis in the Pituitary Gland and Patterns of Death.

BACKGROUND/AIM: We investigated the expression of angiogenesis and hypoxia markers in the adenohypophysis and neurohypophysis of patients who died from various acute or chronic diseases. MATERIALS AND METHODS: Paraffin-embedded material of pituitary glands (97 patients) was investigated immunohistochemically for vascular density (CD31) and the expression of vascular endothelial growth factor (VEGF) and of hypoxia inducible factors HIF1α and HIF2α. RESULTS: Vascular density, and HIF1α/HIF2α reactivity is directly related with VEGF expression in the pituitary gland, suggesting that the HIF pathway may regulate the vascular density and blood flow in the gland under hypoxic conditions. HIF2α appears to be a key regulator in neurohypophysis, whilst in adenohypophysis HIF1α and HIF2α are equally expressed. Chronic conditions, including alcoholism and substance abuse, seem to activate the HIF pathway in both neuro- and adeno-hypophysis. CONCLUSION: The HIF pathway has an important role in regulating vascular density and blood flow in the pituitary gland.

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function.

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation, and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in day length (i.e., photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season (BS), angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication among the PT, PD, and brain. This also acts on VEGF receptor 2 (VEGFR2) expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the BS, melatonin releases antiangiogenic VEGF-Axxxb from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph (LT) VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of LTs, with up-regulation and down-regulation of gonadotrophin gene expression during the breeding and nonbreeding seasons, respectively. These results provide a mechanism by which melatonin can control pituitary function in a seasonal manner.

[PITUITARY ADENOMA APOPLEXY].

We present 3 cases of pituitary adenoma apoplexy in young women (one microadenoma and two macroadenomas). The possible risk factors, clinical presentation and outcome of pituitary apoplexy are discussed. Diagnostic errors as regards pituitary adenoma apoplexy are analyzed.

Clipping Surgery for Paraclinoid Carotid Aneurysm.

BACKGROUND: Paraclinoid carotid aneurysm is widely treated with coil embolization. However, all paraclinoid carotid aneurysms cannot be obliterated by the endovascular approach. METHODS: Our direct surgical procedure was presented. The clinical data of surgically treated paraclinoid carotid aneurysms were retrospectively reviewed. RESULTS: One hundred ninety paraclinoid carotid aneurysms in 181 patients were directly obliterated at the Shinshu University Hospital and its affiliated hospitals between 1991 and 2013. CONCLUSIONS: Direct surgical repair of the paraclinoid carotid aneurysm is still useful, even in the era of endovascular treatment.

Development of syndrome of inappropriate antidiuretic hormone secretion (SIADH) after Onyx embolisation of a cavernous carotid fistula.

Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities.

Long-term hormonal follow-up after human Puumala hantavirus infection.

OBJECTIVE: Nephropathia epidemica (NE) is a haemorrhagic fever with renal syndrome (HFRS) caused by Puumala hantavirus (PUUV). Pituitary haemorrhage and hypopituitarism may complicate recovery from acute NE. DESIGN: Forty-seven of our recent cohort of 58 NE patients volunteered to be re-examined in order to estimate the burden of hormonal deficiency 4 to 8 years after the acute illness. Two patients had suffered from pituitary haemorrhage, but many others exhibited pituitary oedema during their acute infection. In this study, we searched for symptoms of hormonal deficiency, performed hormonal laboratory screening, and most patients underwent pituitary MRI examination. RESULTS: The pituitary size had diminished in all patients in whom MRI was performed (P < 0·001). One patient with acute phase haemorrhage had made a complete recovery while the other continued to require hormonal substitution. In addition, hormonal laboratory abnormalities were observed in nine other patients; these being attributable to several reasons, for example independent peripheral hormonal diseases, side effects of medication or other secondary causes such as obesity. None of them had signs of late-onset pituitary insufficiency caused by their previous NE. Health-related quality of life (mean and median 15D score) of patients was comparable to that of age-standardized general population. CONCLUSIONS: None of our patients had developed obvious late-onset hypopituitarism despite of the fact that pituitary gland can be affected during acute NE. We recommend requesting a history of hantavirus infection whenever the possibility of pituitary dysfunction is suspected at least in patients originating from regions with high NE infection rate.

Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction.

BACKGROUND AND PURPOSE: The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS: A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS: Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS: This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging.

PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development.

We have recently shown that cells positive for the paired-related homeobox transcription factors PRRX1 and PRRX2 occur in the rat pituitary, and that they are derived from two different origins: pituitary-derived cells positive for stem cell marker SOX2 and extra-pituitary-derived cells negative for SOX2. In this study, we have further characterized the PRRX1- and PRRX2-positive cells that originate from extra-pituitary cells. Immunohistochemical analyses were performed with specific antibodies against PRRX1 and PRRX2 in order to clarify their roles in pituitary vasculogenesis. PRRX1- and PRRX2-positive cells were found in Atwell's recess and at the periphery of the pituitary on embryonic day 15.5 (E15.5). Several PRRX1-positive cells then invaded the anterior lobe, together with a few PRRX2-positive cells, on E16.5. Some PRRX1-positive cells were also positive for mesenchymal stem cell marker NESTIN. Moreover, some PRRX1/NESTIN double-positive cells showed characteristics of vascular endothelial cells with an Isolectin-B4-binding capacity. PRRX1 co-localized with vascular smooth muscle cell/pericyte marker α-smooth muscle actin in the deep area of Atwell's recess. We confirmed the presence of PRRX2/NESTIN double-positive cells at an entry area in Atwell's recess and at the periphery of the pituitary, but PRRX2 did not co-localize with Isolectin B4 or α-smooth muscle actin. These data suggest that PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are present at the periphery of the embryonic pituitary and at the entry from Atwell's recess and participate in pituitary vasculogenesis by differentiation into vascular endothelial cells and pericytes, whereas the presence of PRRX2 indicates much higher stemness than PRRX1.