Safe handling of veins in the pineal region-a mixed method study.

Surgical experience in pineal surgery is largely confined to a few experienced surgeons and may be lost when they stop their practice. The objective of this study is to systematically preserve and analyze valuable practical knowledge of pineal region surgical venous anatomy. A survey was constructed to obtain experienced surgeons' perception of estimated risks and individual experience following occlusion of veins during pineal surgery. Data were qualitative and analyzed with a mixed methods approach. Of the 126 invited neurosurgeons, 40 submitted completed questionnaires. General agreement existed of which veins were associated with high and low risks following occlusion. The risk of death was estimated to be high with sacrifice of the vein of Galen (83%), both internal cerebral veins (69%) and the basal veins (58%). The risk of death was estimated to be lower with the sacrifice of both superior vermian veins (13%) and one internal occipital vein (10%). Importantly, a sub-group of experienced surgeons reported substantial risk of death and consequences with the sacrifice of cerebellar bridging veins (8-13%). Our findings provide a coherent picture of surgical risk with venous sacrifice, which can inform the surgical community of systematically gathered views from aggregated surgeries of a very large cohort of patients. Extensive presurgical radiological workup and anatomical studies seemed to correlate more cautious risk estimations. Our findings increase available knowledge of risks of venous complications.

Immunofluorescence reveals unusual patterns of labelling for connexin43 localized to calbindin-D28K-positive interstitial cells in the pineal gland.

Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 µm) or as unusually large pools of Cx43 ranging up to 4-7 µm in diameter or length. These puncta and pools were highly concentrated in perivascular spaces, where they were associated with numerous cells devoid of labelling for markers of pinealocytes (e.g. tryptophan hydroxylase and serotonin), and where they were minimally associated with blood vessels and lacked association with resident macrophages. Astrocytes labelled for glial fibrillary acidic protein were largely restricted to the anterior pole of the pineal gland, where they displayed only fine and sparse Cx43-puncta along their processes. Labelling for Cx43 was localized largely though not exclusively to the somata and long processes of a subpopulation of perivascular interstitial cells that were immunopositive for calbindin-D28K. These cells were often located among dense bundles or termination areas of sympathetic fibres labelled for tyrosine hydroxylase or serotonin. The results indicate that interstitial cells form abundant gap junctions composed of Cx43, and suggest that gap junction-mediated intracellular communication by these cells supports the activities of pinealocytes.

Tumor cells forming sinusoids connected to vasculature are involved in hemorrhage of pineal choriocarcinoma.

Intratumor hemorrhage is a poor prognostic factor in pineal choriocarcinoma (PCCC). The aim of this study was to understand the relationship of tumor cells to the blood vessels to gain insights into the formation of intratumor hemorrhage in PCCC. The clinical data indicated that total tumor removal by surgical procedures followed immediately by radiotherapy and chemotherapy improved the prognosis in PCCC. The PCCC tissues removed from the patients were examined by histology and immunohistochemistry. Hematoxylin and eosin staining showed that the tumor stroma mainly consists of hemorrhagic tissues with tumor cells scattered inside. The pattern of distribution suggests that the tumor cells were possibly flushed and compressed by the bleeding. The tumor cells tended to form sinusoids that lacked CD34, but laminin expression provided evidence of vasculogenic mimicry. Interestingly, CD34-positive blood vessels were found connected to these sinusoids, suggesting that blood may flow from the tumor vasculature to the sinusoids. This may subsequently cause the enlargement of the sinusoids, blood clotting, the widening of the blood lakes, and eventually extensive hemorrhagic necrosis. Our study identified the key features of the PCCC vasculature. The findings add to the previous understanding of the formation of vascular channels, blood lakes, and extensive hemorrhagic necrosis. The intimate connections between the tumor-formed sinusoids and the blood vessels might be a major cause of severe hemorrhage in PCCC. The new information may be useful for the development of treatment strategies for managing PCCC.

Arterial vascularization of the pineal gland.

PURPOSE: The arterial vascularization of the pineal gland (PG) remains a debatable subject. This study aims to provide detailed information about the arterial vascularization of the PG. METHODS: Thirty adult human brains were obtained from routine autopsies. Cerebral arteries were separately cannulated and injected with colored latex. The dissections were carried out using a surgical microscope. The diameters of the branches supplying the PG at their origin and vascularization areas of the branches of the arteries were investigated. RESULTS: The main artery of the PG was the lateral pineal artery, and it originated from the posterior circulation. The other arteries included the medial pineal artery from the posterior circulation and the rostral pineal artery mainly from the anterior circulation. Posteromedial choroidal artery was an important artery that branched to the PG. The arterial supply to the PG was studied comprehensively considering the debate and inadequacy of previously published studies on this issue available in the literature. CONCLUSIONS: This anatomical knowledge may be helpful for surgical treatment of pathologies of the PG, especially in children who develop more pathology in this region than adults.

Vascular Lesions of the Pineal Region: A Comprehensive Review of the Therapeutic Options.

OBJECTIVE: Vascular lesions of the pineal region comprise aneurysms of the pineal region, arteriovenous malformations, cavernous malformations, and vein of Galen malformations. In the present report, we have offered an extensive review of each vascular pineal region lesion. METHODS: We performed an extensive literature review, focusing on the current therapeutic options available for the different vascular lesions of the pineal region. RESULTS: Vascular lesions of the pineal region are rare. Microneurosurgery remains a valid treatment of cavernomas, arteriovenous malformations, and aneurysms. Endovascular treatments seem to be the first option for the vein of Galen malformations, followed by microneurosurgery. Radiosurgery seems beneficial for small-size arteriovenous malformations. Complex and large vascular lesions will require a combination of multiple treatments. CONCLUSIONS: Vascular lesions of the pineal region are complex, uncommon diseases. Thus, definitive therapeutic modalities for these lesions require further research.

Classification of the venous architecture of the pineal gland by 7T MRI.

Magnetic resonance imaging (MRI) at 7.0 Tesla (7T) can show many details of anatomical structures with unprecedented resolution and contrast. In this report, we describe for the first time the unexpected wide variation in pineal gland structure, as visualized by MR images obtained with 7T in a group of healthy young volunteers. A total of 34 volunteers (22 men and 12 women) were enrolled in the study. Their 7T MR images revealed such wide variations in pineal gland shape that it led us to attempt to classify the patterns seen in these pineal glands. Indeed, they were successfully correlated with a previous human cadaver study of venous structures by Tamaki et al., who classified the venous structures of the pineal gland into three categories. This is the first human in vivo pineal vein imaging study using 7T MRI. Pineal venous imaging may permit the early diagnosis of a pineal tumor.

The Anatomy of the Convergence of Major Deep Cerebral Veins in the Pineal Region: A Computed Tomography Angiography Study.

BACKGROUND: The anatomy of the veins in the pineal region is one of the most complex areas in the brain because all major deep cerebral veins converge there: the internal cerebral veins (ICVs), the great cerebral vein of Galen (GV), the basal veins (BVs), and the internal occipital veins (IOVs). The aim of this study was to comprehensively describe the anatomy of the veins in the pineal region using computed tomography angiography. METHODS: Head computed tomography angiography scans of 250 adult Polish patients were evaluated. We assessed the location of the junction of 2 ICVs and the presence of a narrowing of the GV and arachnoid granulation at the GV-straight sinus junction. We evaluated the presence, appearance, and termination of the BV, and the presence and termination of the IOV. RESULTS: The study showed that 2 ICVs usually converged posterior to the splenium of the corpus callosum (62.4%). Narrowing of the BV was observed in 51.2% of patients, and the arachnoid granulation was found in 25.2%. The 3 segments of the BV were well visualized in 66% of the studied hemispheres. The BV flowed into the GV in 34.8% of the hemispheres. The IOV was present in 90.2% of the hemispheres and terminated medially in 84.5%. CONCLUSIONS: Because an injury to major deep cerebral veins may result in severe postoperative neurologic deficits, it is essential for neurosurgeons to be familiar with both normal and variant patterns of veins in the pineal region.

Aquaporin-1 in blood vessels of rat circumventricular organs.

Although the water channel protein aquaporin-1 (AQP1) is widely observed outside the rat brain in continuous, but not fenestrated, vascular endothelia, it has not previously been observed in any endothelia within the normal rat brain and only to a limited extent in the human brain. In this immunohistochemical study of rat brain, AQP1 has also been found in microvessel endothelia, probably of the fenestrated type, in all circumventricular organs (except the subcommissural organ and the vascular organ of the lamina terminalis): in the median eminence, pineal, subfornical organ, area postrema and choroid plexus. The majority of microvessels in the median eminence, pineal and choroid plexus, known to be exclusively fenestrated, are shown to be AQP1-immunoreactive. In the subfornical organ and area postrema in which many, but not all, microvessels are fenestrated, not all microvessels are AQP1-immunoreactive. In the AQP1-immunoreactive microvessels, the AQP1 probably facilitates water movement between blood and interstitium as one component of the normal fluxes that occur in these specialised sensory and secretory areas. AQP1-immunoreactive endothelia have also been seen in a small population of blood vessels in the cerebral parenchyma outside the circumventricular organs, similar to other observations in human brain. The proposed development of AQP1 modulators to treat various brain pathologies in which AQP1 plays a deleterious role will necessitate further work to determine the effect of such modulators on the normal function of the circumventricular organs.

The circumventricular organs: an atlas of comparative anatomy and vascularization.

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Microsurgical Management of Vascular Malformations of the Pineal Region.

BACKGROUND: Vascular pineal malformations are rare and technically demanding lesions. Because the locations of these lesions, endovascular techniques and radiosurgery have been increasingly used in the recent decades to accomplish safe occlusion. Nevertheless, microsurgical treatment may be required sometimes. METHODS: We present a retrospective review of the vascular pineal malformations operated by the senior author. Moreover, we report illustrative cases for the various types of vascular lesions with a careful analysis of the different microsurgical stages. RESULTS: Eighteen patients with pineal vascular lesions were operated on between 1980 and 2015: 6 patients had vein of Galen malformations, 5 plexiform arteriovenous malformations, 6 cavernous malformations, and 1 patient had a ruptured medial posterior choroidal artery aneurysm. A complete resection and occlusion was possible in all vascular malformations. CONCLUSIONS: The pineal region is an infrequent but challenging location for vascular lesions. A careful and stepwise operative strategy for the different types of vascular lesion is paramount to accomplish an effective and safe microsurgical treatment when other alternatives fail or are not available.

Modified Pure Endoscopic Approach to Pineal Region: Proof of Concept of Efficient and Inexpensive Surgical Model Based on Laboratory Dissections.

OBJECTIVE: In recent decades endoscopic techniques have been increasingly used in neurosurgery as they may offer a valuable close-up view of the working area through a minimally invasive surgical corridor. Herein, we present an inexpensive and efficient endoscopic surgical model using a borescope, which was used for a "modified pure endoscopic approach" to the pineal region. METHODS: A borescope video camera was connected to a 16-inch personal computer monitor. A standard midline suboccipital craniotomy was performed on 2 cadaveric heads in the Concorde position. Then, a "borescopic" supracerebellar infratentorial approach was executed, thus reaching the pineal region, which was exposed through an extensive arachnoid dissection. RESULTS: Using the previously described model, we were able to provide excellent exposure of the main neurovascular structures of the pineal region, as shown by the intraoperative videos. In 1 specimen we identified an incidental pineal cyst that was meticulously dissected and removed. CONCLUSIONS: Our proposed "borescopic" surgical model may represent an inexpensive and efficient alternative to conventional endoscopic techniques and could be used for training purposes, as well as even for clinical procedures, after a proper validation, particularly in economically challenging environments.

Identification of venous variants in the pineal region with 3D preoperative computed tomography and magnetic resonance imaging navigation. A statistical study of venous anatomy in living patients.

OBJECT: The purpose of this study was to determine the ability of software-assisted 3D reconstruction performed using a neuronavigation system to delineate the anatomy and variation patterns of the pineal region venous complex, and then to compare these data with previous anatomical findings. METHODS: The authors retrospectively reviewed the neuroimages obtained in 100 patients with intracranial lesions (50 computed tomography [CT] scans obtained with contrast agents and 50 magnetic resonance [MR] images obtained with gadolinium) by using a neuronavigation workstation for 3D reconstruction. Particular attention was given to the internal cerebral vein, basal vein (BV), and the vein of Galen. The various connection patterns between the major vessels were classified and statistically analyzed. CONCLUSIONS: The venous system of the pineal region shows a wide range of sex-related variations. In the female patient the absence of a BV (Type 0) is significantly more frequent than in the male. In this study the authors illustrate the ability to depict the venous drainage patterns in the pineal region for all cases studied by using 3D neuronavigation software without the need for additional examinations. This simple tool provides important information for surgical planning and may be of significant help intraoperatively.

The galenic venous system: surgical anatomy and its angiographic and magnetic resonance venographic correlations.

OBJECTIVE: This study aims at evaluating the adequacy of digital subtraction angiography and magnetic resonance venography in imaging of the galenic venous system for surgical planning of approaches to the pineal region. Anatomical dissections were carried out in 10 cadavers of several age groups and these were compared to imaging findings in 10 living subjects. METHODS: The presence or absence of 10 predetermined veins or vein groupings belonging to the galenic venous system were prospectively analyzed in 10 cadaver dissections and imaging findings of 10 age matched human subjects. The studied vessels were the vein of galen, the internal cerebral veins, both basal vein of Rosenthals, internal occipital vein, occipitotemporal veins, precentral cerebellar veins, tectal veins, pineal veins, superior vermian veins (including superior cerebellar veins (SCVs)) and posterior pericallosal veins. Each of the subjects had both digital subtraction angiography and magnetic resonance venography studies performed. Diagnostic digital subtraction angiography was performed using the transfemoral route and the venous phase was used for the study. Magnetic resonance venography was performed in 1.5 T MRI equipment using the 2D-TOF sequence. All studies were reported to be normal. RESULTS: There was wide variation in the anatomy of the galenic venous system. There were interpersonal, intrapersonal and age related variations. Both the digital subtraction angiography and the magnetic resonance venography were efficient at demonstrating large veins. However, smaller veins were less readily demonstrated in either study. The general sensitivities of the digital subtraction angiography and the magnetic resonance venography for the galenic venous system were 45.5% and 32.5%, respectively. Surgically important veins were missed in most studies. CONCLUSIONS: Anatomically, the galenic venous system is highly variable. This variability is caused by interpersonal, intrapersonal and age related differences and causes each individual galenic venous system to be unique. Therefore, modern neurosurgical procedures require anatomical information on individual differences. Current radiological methods of digital subtraction angiography and magnetic resonance venography fail short of providing the necessary information. New and more sophisticated MRI technology may fulfill this need.

Pineal cavernous malformations: report of two cases.

Pineal hemorrhage only occurs in rare cases, and this known to have several different causes such as germ cell tumors, pineal cysts and vascular malformations, including the cavernous malformations. Pineal cavernous malformations are extremely rare: to date only fifteen cases have been reported worldwide. Although the diagnosis of pineal cavernous malformation is not easy because of the extreme rareness of this condition, the presence of this lesion can be suspected based on its typical radiological findings. Case 1. A 42-year- old man presented with a limitation in his upward gazing. Radiologic examinations showed acute hemorrhage in the pineal region. He underwent ventriculo-peritoneal (VP) shunting but the patient's condition deteriorated after the shunting surgery. We operated and totally removed the tumor and the hemorrhages via an occipital-transtentorial approach. Case 2. A 37-year-old man presented with diplopia. Radiologic examinations showed acute hemorrhage in the third ventricle. He underwent VP shunting, and after this procedure the diplopia was aggravated. We operated and totally removed the tumor and the hemorrhages via an occipital-transtentorial approach. If there is no doubt about the pineal cavernous malformation on MR imaging, we strongly recommend early surgical intervention without performing a risky biopsy. In this study, we describe our experiences for the diagnosis of cavernous malformations in the pineal region with special emphasis on the radiological aspects and the clinical course of this disease.

Autonomic nerves terminating on microvessels in the pineal organs of various submammalian vertebrates.

In earlier works we have found that in the mammalian pineal organ, a part of autonomic nerves--generally thought to mediate light information from the retina--form vasomotor endings on smooth muscle cells of vessels. We supposed that they serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. In the present work, we investigated whether peripheral nerves present in the photoreceptive pineal organs of submammalians form similar terminals on microvessels. In the cyclostome, fish, amphibian, reptile and bird species investigated, autonomic nerves accompany vessels entering the arachnoidal capsule and interfollicular meningeal septa of the pineal organ. The autonomic nerves do not enter the pineal tissue proper but remain in the perivasal meningeal septa isolated by basal lamina. They are composed of unmyelinated and myelinated fibers and form terminals around arterioles, veins and capillaries. The terminals contain synaptic and granular vesicles. Comparing various vertebrates, more perivasal terminals were found in reptiles and birds than in the cyclostome, fish and amphibian pineal organs. Earlier, autonomic nerves of the pineal organs were predominantly investigated in connection with the innervation of pineal tissue. The perivasal terminals found in various submammalians show that a part of the pineal autonomic fibers are vasomotoric in nature, but the vasosensor function of some fibers cannot be excluded. We suppose that the vasomotor regulation of the pineal microvessels in the photosensory submamalian pineal--like in mammals--may serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. The higher number of perivasal terminals in reptiles and birds may correspond to the higher metabolic activity of the tissues in more differentiated species.

Anatomy of the pineal region applied to its surgical approach.

INTRODUCTION: The pineal region is situated in the posterior part of the incisural space. This region includes the pineal body inside the quadrigeminal arachnoidal cistern. This article reviews the anatomic features of this region, with particular emphasis on those aspects of importance for surgical access to the pineal region. MATERIAL & METHODS: Five cadaver heads fixed in 10% formalin and injected with colored latex were used for anatomic dissection (five other specimens were also prepared and dissected to illustrate the articles on surgical techniques and approaches presented elsewhere in this issue). RESULTS: The pineal body is surrounded by several important structures such as: posterior part of the third ventricle, tectum, the complex of the great cerebral vein of Galen, pulvinar nuclei of the thalamus and splenium of corpus callosum. CONCLUSION: The surgical approach of the pineal body, whatever the route or the technique used (microsurgical, endoscopic or stereotactic), creates a great challenge for the neurosurgeons due to its location in the deep part of the brain and its close relationships with complex surrounded vascular structures.

Effect of hypothalamic deafferentation on hypophysial and other endocrine gland blood flows.

The effects of partial or complete deafferentation of the medical basal hypothalamus (MBH) on blood flow through endocrine glands was evaluated using a modification of Sapirstein's indicator fractionation method. Adult female Wistar rats were distributed into three groups consisting of normal control animals (n = 12), animals in which rostral deafferentation (Rd) of the MBH was performed (n = 11), and animals in which complete deafferentation (Cd) of the MBH was done (n = 6). Three weeks after the surgical procedures, Cd reduced adenohypophysial weight by 30% and raised its blood flow levels by 80% compared to those values in the Rd and control groups. In contrast to the anterior pituitary, both Rd and Cd led to weight reduction of 22% in posterior lobes, and Cd was also accompanied by a 50% net blood flow decrease. No statistically significant differences were noted in pineal gland weights or decreases in blood perfusion rates in adrenal and thyroid glands. There were no body weight changes in experimental animals compared to values in the control groups. These results suggest that there may be a loss of vasomotor tone in the primary vascular beds of the adenohypophysial portal systems after deafferentation which elicits the 80% increase in adenohypophysial blood flow. This increased circulation may play a role in pituitary function(s) and should be included along with diminished neuroendocrine inputs in interpretations of results obtained after deafferentation procedures.

Anionic sites on the luminal surface of fenestrated and continuous capillaries of the CNS.

We injected intravenously cationic ferritin, pI 8.4, and studied patterns of labeling of the luminal surface of capillaries in the CNS of rats. Cationic ferritin consistently labeled the luminal aspect of the diaphragms of fenestrated capillaries in the choroid plexus, median eminence and pineal. No other feature of these endothelial cells was consistently labeled. Diaphragms spanning the mouths of vesicles open to the lumen were not labeled. Occasional ferritin molecules were seen in the BL of these fenestrated vessels. The luminal surfaces of endothelial cells of the continuous capillaries of the brain, and of reactive capillaries proliferating in a region of cold injury necrosis, were not labeled. Ferritin was not seen in cytoplasmic structures or the basal lamina of these vessels. The findings in the fenestrated capillaries of CNS are in agreement with those reported for other fenestrated endothelia. The absence of labeling of the continuous capillaries of the blood-brain barrier differs from findings reported for other continuous capillaries, with the exception of the blood-air barrier portions of lung capillaries.

Potential role of kallikrein in diurnal rhythms and perivascular distribution in rat pineal glands.

Kallikrein hydrolyzes various biologically active peptides, other than kininogens, such as vasoactive intestinal polypeptide (VIP), in vitro. Since kallikrein and VIP have been immunohistochemically shown to be present in the perivascular areas of the pineal gland, this study was designed to determine their topographic proximity in these glands, using immunohistochemical and immunoelectron microscopic double staining methods. Furthermore, since this gland is well-known to have a circadian rhythm, the kallikrein content was measured every 4 h, using a synthetic substrate, Pro-Phe-Arg-MCA, and an enzyme-linked immunosorbent assay (ELISA) to determine whether kallikrein has a circadian rhythm. The immunoreactivities of kallikrein and VIP were highly localized in the perivascular extracellular spaces and were virtually identical in distribution. The kallikrein content changed every 4 h and was high under light and low under dark conditions. The change was more evident when the synthetic substrate was used, and this rhythm was subtle on ELISA. VIP is also said to have a circadian rhythm in the pineal glands, being low under light and high under dark conditions, i.e., opposite to that of kallikrein. Since kallikrein degrades VIP in vitro, it is reasonable to speculate that pineal gland kallikrein is involved in the processing of VIP and possibly other biologically active peptides in the perivascular areas with a discernible circadian rhythm.