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.

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.

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.

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.

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.

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.

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.

Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces.

Historically, the direct release of pineal melatonin into the capillary bed within the gland has been accepted as the primary route of secretion. Herein, we propose that the major route of melatonin delivery to the brain is after its direct release into the cerebrospinal fluid (CSF) of the third ventricle (3V). Melatonin concentrations in the CSF are not only much higher than in the blood, also, there is a rapid nocturnal rise at darkness onset and precipitous decline of melatonin levels at the time of lights on. Because melatonin is a potent free radical scavenger and antioxidant, we surmise that the elevated CSF levels are necessary to combat the massive free radical damage that the brain would normally endure because of its high utilization of oxygen, the parent molecule of many toxic oxygen metabolites, i.e., free radicals. Additionally, the precise rhythm of CSF melatonin provides the master circadian clock, the suprachiasmatic nucleus, with highly accurate chronobiotic information regarding the duration of the dark period. We predict that the discharge of melatonin directly into the 3V is aided by a number of epithalamic structures that have heretofore been overlooked; these include interpinealocyte canaliculi and evaginations of the posterodorsal 3V that directly abut the pineal. Moreover, the presence of tanycytes in the pineal recess and/or a discontinuous ependymal lining in the pineal recess allows melatonin ready access to the CSF. From the ventricles melatonin enters the brain by diffusion and by transport through tanycytes. Melatonin-rich CSF also circulates through the aqueduct and eventually into the subarachnoid space. From the subarachnoid space surrounding the brain, melatonin penetrates into the deepest portions of the neural tissue via the Virchow-Robin perivascular spaces from where it diffuses into the neural parenchyma. Because of the high level of pineal-derived melatonin in the CSF, all portions of the brain are better shielded from oxidative stress resulting from toxic oxygen derivatives.

A hemorrhagic pineal cyst with a bacterial meningitis-like manifestation and benign outcome.

Pineal cysts are a common incidental finding in imaging studies, and the majority of such cysts are asymptomatic. However, hemorrhaging pineal cysts, which are considered to be rare, are often associated with severe symptoms. We herein describe the case of a 58-year-old patient with the novel manifestation of a bleeding pineal cyst, who had a benign outcome without any surgical treatment. Although the clinical manifestations resembled those of bacterial meningitis, magnetic resonance images suggested chemical meningitis caused by an intracystic hemorrhage and rupture of the pineal cyst.

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.

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.

Identification of venous variants in the pineal region with three-dimensional preoperative magnetic resonance imaging navigation in patients harbouring tumors in this area: significance for surgical approach to the lesion.

OBJECT: The purpose of this study was to identify the anatomy of pineal region venous complex using neuronavigation software when distorted by the presence of a space-occupying lesion and to describe the anatomical relationship between lesion and veins. Moreover we discuss its influence on the choice of the surgical strategy. METHODS: Of the 33 patients treated at our Institute for pineal region tumors between 2003 and 2008 we used the neuronavigation software to depict the venous system of the pineal region in 14 patients. We focused on depiction of the basal vein of Rosenthal (BV), the internal cerebral vein (ICV) and the vein of Galen: connection patterns between the veins and the type of anatomical distortion caused by the lesion were investigated and classified. RESULTS: Using the neuronavigation software for three-dimensional (3D) reconstruction of MRI images the ICV was clearly depicted in all patients on both sides (100%). Last segment of the BV was identified in 25 sides on a total of 28 (89.3%) and absent in 3 of the 28 sides (10.7%). Studying the distortion effect of the tumor on the galenic venous system, three directions of displacement were observed: craniocaudal, anteroposterior and lateral. Seven patients presented a cranial dislocation, 5 patients caudal dislocation and there was no craniocaudal shift in 2 patients. Considering the anteroposterior displacement: 3 subjects showed an anterior shift of the veins, 5 subjects posterior shift and no anterioposterior shift was present in 6 patients. Only 2 of the 14 patients presented lateral displacement of the veins. The principal approaches used in this series were: supracerebellar infratentorial and interhemispheric parieto-occipital. The craniocaudal displacement of the pineal veins seems to be the most important for the choice of the approach. CONCLUSION: The galenic venous system has a central role in the surgery pineal region tumors. Our study demonstrates that the architecture of the pineal veins and their anatomical relationship with the lesion can be depicted with great accuracy by using 3D neuronavigation software in order to facilitate surgical planning and intraoperative orientation.

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.

Distribution of components of basal lamina and dystrophin-dystroglycan complex in the rat pineal gland: differences from the brain tissue and between the subdivisions of the gland.

The pineal gland is an evagination of the brain tissue, a circumventricular neuroendocrine organ. Our immunohistochemical study investigates basal lamina components (laminin, agrin, perlecan, fibronectin), their receptor, the dystrophin-dystroglycan complex (beta-dystroglycan, dystrophin utrophin), aquaporins (-4,-9) and cellular markers (S100, neurofilament, GFAP, glutamine synthetase) in the adult rat corpus pineale. The aim was to compare the immunohistochemical features of the cerebral and pineal vessels and their environment, and to compare their features in the distal and proximal subdivisions of the so-called 'superficial pineal gland'. In contrast to the cerebral vessels, pineal vessels proved to be immunonegative to alpha1-dystrobrevin, but immunoreactive to laminin. An inner, dense, and an outer, loose layer of laminin as two basal laminae were present. The gap between them contained agrin and perlecan. Basal lamina components enmeshed the pinealocytes, too. Components of dystrophin-dystroglycan complex were also distributed along the vessels. Dystrophin, utrophin and agrin gave a 'patchy' distribution rather than a continuous one. The vessels were interconnected by wing-like structures, composed of basal lamina-components: a delicate network forming nests for cells. Cells immunostained with glutamine synthetase, S100-protein or neurofilament protein contacted the vessels, as well as GFAP- or aquaporin-immunostained astrocytes. Within the body a smaller, proximal, GFAP-and aquaporin-containing subdivision, and a larger, distal, GFAP-and aquaporin-free subdivision could be distinguished. The vascular localization of agrin and utrophin, as well as dystrophin, delineated vessels unequally, preferring the proximal or distal end of the body, respectively.

Depiction of small veins draining into the vein of galen using preoperative 3-dimensional navigation in living patients.

OBJECTIVE: The purpose of this study was to delineate the anatomy of the precentral cerebellar vein, superior vermian vein, and internal occipital vein using reconstructions of computed tomographic and magnetic resonance imaging scans with navigation software. These data were compared with previous anatomic and angiographic findings to show the resolution and accuracy of the system. METHODS: We retrospectively reviewed 100 patients with intracranial pathologies (50 computed tomographic scans with contrast and 50 magnetic resonance imaging scans with gadolinium) using a neuronavigation workstation for 3-dimensional reconstruction. Particular attention was paid to depiction of the precentral cerebellar vein, superior vermian vein, and internal occipital vein. The data were reviewed and analyzed. RESULTS: The precentral cerebellar vein, superior vermian vein, and its tributary, the supraculminate vein, were depicted in 52 (52%) patients. The internal occipital vein was delineated on 99 (49.5%) sides and joined the basal vein and vein of Galen in 39 (39.4%) and 60 (60.6%) hemispheres, respectively. Comparing these results with previous angiographic studies, the ability of the neuronavigation system for depicting these vessels is similar to that of digital subtraction angiography. CONCLUSION: This study illustrates the possibility of depicting the small vessels draining into the pineal region venous complex using 3-dimensional neuronavigation with an accuracy comparable to that of digital subtraction angiography. This tool provides important information for both surgical planning and intraoperative orientation.

[Worsening of migraine symptoms due to giant pineal cyst apoplexy]. / Agravamiento de un cuadro migrañoso por apoplejía de un quiste pineal gigante.

INTRODUCTION: Although the association between headaches and pineal gland cysts has been suggested on a number of occasions, no precise evidence of exactly what this relation involves has been produced to date. It is known, however, that a cyst in the pineal gland can bring on or worsen headaches, especially if it is large or there has been bleeding, due to obstructive compromise in the third ventricle and the resulting hydrocephalus that is produced. CASE REPORT: A 15 years-old male who had suffered from migraine from the age of 6 years and who suddenly experienced a worsening of his headaches, both as regards their frequency and their intensity, over the previous days; no known precipitating factor appeared to be involved. Magnetic resonance imaging of the brain revealed the presence of a giant cyst in the pineal gland, with a notable amount of blood inside it, which was producing an obstructive hydrocephalus. The decision was made to resort to surgical treatment, with resection of the cyst and placement of a shunt valve. As a result the patient's headaches improved greatly and this improvement continued throughout a six-month follow-up. CONCLUSIONS: Worsening of a headache, in this case migraine, for no apparent cause must make us consider secondary processes, although they may be as rare as the one described here.

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.