The Roof of the 4th Ventricle Seen From Inside: Endoscopic Anatomic Illustration-A Case Series.

BACKGROUND: The anatomy of the roof of the fourth ventricle has been illustrated in many laboratory investigations, but in vivo reports of the roof anatomy and its variants are still lacking. OBJECTIVE: To describe the topographical anatomy of the roof of the fourth ventricle explored through a transaqueductal approach that overcomes cerebrospinal fluid depletion, displaying in vivo anatomic images possibly quite close to normal physiological conditions. METHODS: We critically reviewed the intraoperative video recordings of our 838 neuroendoscopic procedures, selecting 27 cases of transaqueductal navigation that provided good quality image details of the anatomy of the roof of the fourth ventricle. Twenty-six patients affected by different forms of hydrocephalus were therefore categorized into three groups: Group A: blockage of the aqueduct-aqueductoplasty, Group B: communicating hydrocephalus, and Group C: tetraventricular obstructive hydrocephalus. RESULTS: Group A has shown what the roof of a normal fourth ventricle really looks like albeit the structures seemed overcrowded because of the narrow space. Images from groups B and C paradoxically allowed a more distinct identification of the roof structures flattened by ventricular dilation, making them more comparable with the topography traced on the laboratory microsurgical studies. CONCLUSION: Endoscopic in vivo videos and images provided a novel anatomic view and an in vivo redefinition of the real topography of the roof of the fourth ventricle. The relevant role of cerebrospinal fluid was defined and outlined, as well as the effects of hydrocephalic dilation on some structures on the roof of the fourth ventricle.

How I do it: flexible endoscopic aspiration of intraventricular hemorrhage.

BACKGROUND: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension. METHOD: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained. CONCLUSION: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency.

New perspectives in the endoscopic treatment of brain purulent collections: targets, techniques, results in a case series, and overview of the literature.

BACKGROUND: Purulent intracranial infections are threatening conditions. Different surgical approaches have been described, respecting the rationale of evacuating the fluid component of the purulent collection. Emerging evidence supports the use of the endoscope for the treatment of cerebral abscesses and subdural empyemas; especially the peculiarities of flexible endoscopes could potentially offer a more effective and conclusive management as compared with the drainage through catheters. We describe our experience in the treatment of intracranial purulent collections with flexible endoscopy, comparing it with the most recent literature. METHODS: Ten patients affected by intracranial suppuration were treated with endoscopy at our institution. The neurosurgical technique is thoroughly described. The related literature is reviewed, providing a comprehensive overview on the endoscopic treatment of intracranial suppuration so far. RESULTS: All the patients had a good clinical outcome, with no peri-operative complications. The postoperative scans showed significant radiological improvement, with important reduction of the pus volume. In all cases, the microbiological cultures showed positivity. CONCLUSIONS: In our experience, the use of the flexible scope proved feasible and effective in the treatment of intracranial purulent collections. Visual awareness of the internal capsule is not limited to a direct inspection of the fluid pus; it rather allows an active removal of the more solid (and perhaps more microbiologically significant) fibrinoid component, and also assists in final bleeding control and in assessing the extent of the evacuation. The steering capabilities of the fiberscope are particularly suitable for such purposes, allowing sampling the solid internal layer of the pyogenic membrane, and potentially shedding light on the actual clinical significance of this component of the abscess.

Form follows function: estimation of CSF flow in the third ventricle-aqueduct-fourth ventricle complex modeled as a diffuser/nozzle pump.

OBJECTIVE: In the last 20 years, researchers have debated cerebrospinal fluid (CSF) dynamics theories, commonly based on the classic bulk flow perspective. New hypotheses do not consider a possible hydraulic impact of the ventricular morphology. The present study investigates, by means of a mathematical model, the eventual role played by the geometric shape of the "third ventricle-aqueduct-fourth ventricle" complex in CSF circulation under the assumption that the complex behaves like a diffuser/nozzle (DN) pump. METHODS: DN pumps are quite recent devices introduced as valveless micropumps in various industrial applications given their property of driving net flow when subjected to rhythmic pulsations. A novel peculiar DN pump configuration was adopted in this study to mimic the ventricular complex, with two reservoirs (the ventricles) and one tube provided with a conical reach (the aqueduct-proximal fourth ventricle). The flow was modeled according to the classic equations of laminar flow, and the external rhythmic pulsations forcing the system were reproduced as a pulsatile pressure gradient between the chambers. Several physiological scenarios were implemented with the integration of data acquired by MRI in 10 patients with no known pathology of CSF dynamics, and a quantitative analysis of the effect of geometric and hydraulic parameters (diverging angle, sizes, frequency of pulsations) on the CSF net flow was performed. RESULTS: The results showed a craniocaudal net flow in all the given values, consistent with the findings of cine MRI studies. Moreover, the net flow estimated for the analyzed cohort of patients ranged from 0.221 to 0.505 ml/min, remarkably close to the values found on phase contrast cine MRI in healthy subjects. Sensitivity analysis underlines the pivotal role of the DN configuration, as well as of the frequency of forcing pressure, which promotes a relevant net flow considering both the heart and respiration rate. CONCLUSIONS: This work suggests that the geometry of the third ventricle-aqueduct-fourth ventricle complex, which resembles a diverter, appears to be functional in the generation of a net craniocaudal flow and potentially has an impact on CSF dynamics. These conclusions can be drawn by observing the analogies between the shape of the ventricles and the geometry of DN pumps and by recognizing the basis of the mathematical model of the simplified third ventricle-aqueduct-fourth ventricle complex proposed.

The human area postrema: clear-cut silhouette and variations shown in vivo.

OBJECT The human area postrema (AP) is a circumventricular organ that has only been described in cadaveric specimens and animals. Because of its position in the calamus scriptorius and the absence of surface markers on the floor of the fourth ventricle, the AP cannot be clearly localized during surgical procedures. METHODS The authors intravenously administered 500 mg fluorescein sodium to 25 patients during neuroendoscopic procedures; in 12 of these patients they explored the fourth ventricle. A flexible endoscope equipped with dual observation modes for both white light and fluorescence was used. The intraoperative fluorescent images were reviewed and compared with anatomical specimens and 3D reconstructions. RESULTS Because the blood-brain barrier does not cover the AP, it was visualized in all cases after fluorescein sodium injection. The AP is seen as 2 coupled leaves on the floor of the fourth ventricle, diverging from the canalis centralis medullaris upward. Although the leaves normally appear short and thick, there can be different morphological patterns. Exploration using the endoscope's fluorescent mode allowed precise localization of the AP in all cases. CONCLUSIONS Fluorescence-enhanced inspection of the fourth ventricle accurately identifies the position of the AP, which is an important landmark during surgical procedures on the brainstem. A better understanding of the AP can also be valuable for neurologists, considering its functional role in the regulation of homeostasis, emesis, and cardiovascular and electrolyte balance. Despite the limited number of cases in this report, evidence indicates that the normal anatomical appearance of the AP is that of 2 short and thick leaves that are joined at the midline. However, there can be great variability in terms of the structure's shape and size.

Third ventriculostomy site as a neuroreceptorial area.

PURPOSE: Endoscopic third ventriculostomy is an established method for treating hydrocephalus. The third ventriculostomy site is considered a safe area that can be disrupted during surgical endoscopic procedures. The question of the clinical consequences of an apparently unavoidable injury to the floor of the third ventricle has been sporadically addressed in the literature. The aim of this study is to describe our anatomical and operative findings during endoscopic procedures performed in fluorescent mode after intravenous fluorescein injection and address the possible role of fluorescein-enhanced visualization of the median eminence as an accessory tool in order to partially spare this functional structure when performing ventriculostomy. METHODS: We prospectively administered intravenously 500 mg of fluorescein sodium in 12 consecutive endoscopic surgery cases. A flexible scope equipped with dual observation modes for both white light and fluorescence was used. Taking into account the position of the basilar apex and the need for a conveniently sized stoma, a perforation area was chosen and dilated using a Fogarty balloon, guided by fluorescein-enhanced visualization of the median eminence. RESULTS: After a mean of 20 s in the fluorescent mode, the fluorescein enhanced the visualization of the median eminence-tuber cinereum complex. In our preliminary experience, by opening the stoma in the fluorescence mode, almost half of the visible median eminence surface can be spared from iatrogenic sacrifice. CONCLUSIONS: Tailoring fluorescence-guided ventriculostomy is a feasible way of trying to preserve the median eminence and may have implications for the site and safety of this common surgical procedure.

Fluorescein-enhanced characterization of additional anatomical landmarks in cerebral ventricular endoscopy.

BACKGROUND: Fluorescein enhancement to detect retinal disorder or differentiate cancer tissue in situ is a well-defined diagnostic procedure. It is a visible marker of where the blood-brain barrier is absent or disrupted. Little is reported in the contemporary literature on endoscopic fluorescein-enhanced visualization of the circumventricular organs, and the relevance of these structures as additional markers for safe ventricular endoscopic navigation remains an unexplored field. OBJECTIVE: To describe fluorescein sodium-enhanced visualization of circumventricular organs as additional anatomic landmarks during endoscopic ventricular surgery procedures. METHODS: We prospectively administered intravenously 500 mg fluorescein sodium in 12 consecutive endoscopic surgery patients. A flexible endoscope equipped with dual observation modes for both white light and fluorescence was used. During navigation from the lateral to the fourth ventricle, the endoscopic anatomic landmarks were first inspected under white light and then under the fluorescent mode. RESULTS: After a mean of 20 seconds in the fluorescent mode, the fluorescein enhanced visualization of the choroid plexus of the lateral ventricle, median eminence-tuber cinereum complex, organum vasculosum of the lamina terminalis, choroid plexus of the third and fourth ventricles, and area postrema. CONCLUSION: Fluorescein-enhanced visualization is a useful tool for helping neuroendoscopists recognize endoscopic anatomic landmarks. It could be adopted to guide orientation when the surgeon deems an endoscopic procedure unsafe or contraindicated because of unclear or subverted anatomic landmarks. Visualization of the circumventricular organs could add new insight into the functional anatomy of these structures, with possible implications for the site and safety of third ventriculostomy.

Endoscopic management of intracerebral hemorrhage.

OBJECTIVES: Massive intracerebral and intraventricular hemorrhages require aggressive and rapid management to decrease intracranial hypertension. The amount of intraventricular blood is a strong prognostic predictor, and its fast removal is a priority. Neuroendoscopy may offer some advantages over more traditional surgical approaches. METHODS: All relevant data described in our experience and in publications about minimally invasive treatment of intraventricular and intracerebral hemorrhage found through MEDLINE searches and related references are reviewed. RESULTS: We described the technical details of neuroendoscopic management, highlighting the potential pitfalls and advantages of the techniques. CONCLUSION: Early neuroendoscopic surgery is a feasible approach, allowing, in most instances, rapid clinical and radiological improvement.

Longitudinal in vivo monitoring of rodent glioma models through thinned skull using laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) is a contrast agent free imaging technique suited for longitudinal assessment of vascular remodeling that accompanies brain tumor growth. We report the use of LSCI to monitor vascular changes in a rodent glioma model. Ten rats are inoculated with 9L gliosarcoma cells, and the angiogenic response is monitored five times over two weeks through a thinned skull imaging window. We are able to visualize neovascularization and measure the number of vessels per unit area to assess quantitatively the microvessel density (MVD). Spatial spread of MVD reveals regions of high MVD that may correspond to tumor location. Whole-field average MVD values increase with time in the tumor group but are fairly stable in the control groups. Statistical analysis shows significant differences in MVD values between the tumor group and both saline-receiving and unperturbed control groups over the two-week period (p<0.05). In conclusion, LSCI is suitable for investigation of tumor angiogenesis in rodent models. In addition, the statistical difference (p<0.02) between MVD values of the tumor (24.40 ± 1.41) and control groups (15.40 ± 1.60) on the 14th day after inoculation suggests a potential use of LSCI in the clinic in distinguishing tumor environments from normal vasculature.

External ventricular drainage alone versus endoscopic surgery for severe intraventricular hemorrhage: a comparative retrospective analysis on outcome and shunt dependency.

OBJECT: Massive intraventricular hemorrhages (IVHs) require aggressive and rapid management to decrease intracranial hypertension, because the amount of intraventricular blood is a strong negative prognostic predictor on outcome. Neuroendoscopy may offer some advantages over more traditional surgical approaches on outcome and may decrease the number of shunt procedures that need to be performed. METHODS: The authors retrospectively reviewed the clinical and radiological data in 96 patients treated for massive IVH who were admitted between January 1996 and June 2008 to the neurosurgery unit after undergoing emergency CT scanning. Forty-eight patients (Group A) were treated with endoscopic aspiration surgery using a flexible endoscope with a "freehand" technique. A historical group of 48 patients (Group B) treated using external ventricular drain (EVD) placement alone was used as a comparison. The authors compared the radiological results with the clinical outcomes at 1 year according to the modified Rankin Scale and the need for internal CSF shunt treatment in the 2 groups. RESULTS: Endoscopic aspiration did not significantly affect the outcome at 1 year as determined using the modified Rankin Scale. Patients who underwent endoscopy had an EVD in place for 0.18 days fewer than patients treated with an EVD alone. Patients undergoing external ventricular drainage alone had a 5 times greater chance of requiring a shunting procedure than those treated using neuroendoscopy and external ventricular drainage. Neuroendoscopy plus external drainage reduces shunting rates by 34% when compared with external drainage alone. CONCLUSIONS: The reduction in internal shunt surgery encourages the adoption of neuroendoscopic aspiration of severe IVH as a therapeutic tool to decrease shunt dependency.

Spontaneous resolution of atraumatic intrauterine ping-pong fractures in newborns delivered by cesarean section.

Two cases of spontaneous intrauterine ping-pong fractures are reported in newborns delivered by cesarean section. Skull fractures occurred with no evidence of extrinsic trauma or cephalopelvic disproportion. Subsequent clinical follow-up at 6 and 12 months revealed normal skull reshaping and growth, with no associated neurological deficits. Spontaneous intrauterine ping-pong fractures in newborns delivered by cesarean section is a distinctly rare condition. These 2 cases demonstrate that, even without complicated spontaneous vaginal delivery or history of external trauma, congenital ping-pong fracture of the skull can occur. The existence of this clinical condition and its spontaneous resolution is important knowledge that can assist in the prepartum and postpartum management of children with this pathology.

Intracranial microcapsule drug delivery device for the treatment of an experimental gliosarcoma model.

Controlled-release drug delivery systems are capable of treating debilitating diseases, including cancer. Brain cancer, in particular glioblastoma multiforme (GBM), is an extremely invasive cancer with a dismal prognosis. The use of drugs capable of crossing the blood-brain barrier has shown modest prolongation in patient survival, but not without unsatisfactory systemic, dose-limiting toxicity. Among the reasons for this improvement include a better understanding of the challenges of delivery of effective agents directly to the brain tumor site. The combination of carmustine delivered by biodegradable polyanhydride wafers (Gliadel(®)), with the systemic alkylating agent, temozolomide, allows much higher effective doses of the drug while minimizing the systemic toxicity. We have previously shown that locally delivering these two drugs leads to further improvement in survival in experimental models. We postulated that microcapsule devices capable of releasing temozolomide would increase the therapeutic capability of this approach. A biocompatible drug delivery microcapsule device for the intracranial delivery of temozolomide is described. Drug release profiles from these microcapsules can be modulated based on the physical chemistry of the drug and the dimensions of the release orifices in these devices. The drug released from the microcapsules in these experiments was the clinically utilized chemotherapeutic agent, temozolomide. In vitro studies were performed in order to test the function, reliability, and drug release kinetics of the devices. The efficacy of the temozolomide-filled microcapsules was tested in an intracranial experimental rodent gliosarcoma model. Immunohistochemical analysis of tissue for evidence of DNA strand breaks via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. The experimental release curves showed mass flow rates of 36 µg/h for single-orifice devices and an 88 µg/h mass flow rate for multiple-orifice devices loaded with temozolomide. In vivo efficacy results showed that localized intracranial delivery of temozolomide from microcapsule devices was capable of prolonging animal survival and may offer a novel form of treatment for brain tumors.

A preliminary study of aquaporin 1 immunolocalization in chronic subdural hematoma membranes.

Aquaporin 1 (AQP1) is a molecular water channel expressed in many anatomical locations, particularly in epithelial barriers specialized in water transport. The aim of this study was to investigate AQP1 expression in chronic subdural hematoma (CSDH) membranes. In this preliminary study, 11 patients with CSDH underwent burr hole craniectomy and drainage. Membrane specimens were stained with a monoclonal antibody targeting AQP1 for immunohistochemical analysis. The endothelial cells of the sinusoid capillaries of the outer membranes exhibited an elevated immunoreactivity to AQP1 antibody compared to the staining intensity of specimens from the inner membrane and normal dura. These findings suggest that the outer membrane might be the source of the increased fluid accumulation responsible for chronic hematoma enlargement.

Endoscopic third ventriculostomy in previously shunted children: a retrospective study.

PURPOSE: The aim of this study was to assess the mid-term results, success rates, and time-to-failure of secondary endoscopic third ventriculostomy (secondary ETV), as well as the complex management of preoperative and postoperative cares. METHODS: To this purpose, a retrospective analysis of a pediatric population of 22 children who underwent endoscopic third ventriculostomy (ETV) after shunt malfunction (secondary ETV) was performed. RESULTS: The failure rate, given by the percentage of new shunt replacement in the first 3 months after ETV, was 36%, with a mean time to failure of 14.3 days. All the failures were evident within 1 month after the ETV. Despite the small number of patients in our series, we found no significant correlation between ETV failure and both patient age and hydrocephalus etiology (p = 0.47 and p = 0.78, respectively). CONCLUSIONS: In our experience, ETV secondary to shunt malfunction in pediatric patients has a success rate of 64%. As it is a safe and rapid treatment option even in emergency conditions, it is worth performing this procedure in previously shunted children.

A thermal gel depot for local delivery of paclitaxel to treat experimental brain tumors in rats.

OBJECT: Paclitaxel, a cellular proliferation inhibitor/radiation sensitizer, while effective against gliomas in vitro, has poor CNS penetration and dose-limiting toxicities when administered systemically. OncoGel (paclitaxel in Re-Gel) provides controlled local paclitaxel release when placed into the CNS. The authors evaluated the safety and efficacy of OncoGel in rats with intracranial 9L gliosarcoma. METHODS: Safety studies included intracranial delivery of increasing volumes of ReGel and OncoGel containing 1.5 (OncoGel 1.5) or 6.3 (OncoGel 6.3) mg/ml paclitaxel. An in vivo radiolabeled biodistribution study was performed in 18 Fischer-344 rats to determine intracerebral distribution. Efficacy studies compared overall survival for controls, ReGel only, radiation therapy only, OncoGel 6.3, or OncoGel 6.3 in combination with radiation therapy. ReGel and OncoGel 6.3 were delivered either simultaneously with tumor implantation (Day 0) or 5 days later (Day 5). Radiation therapy was given on Day 5. RESULTS: Control and ReGel animals died of tumor within 17 days. Survival significantly increased in the Onco-Gel 6.3 group on Day 0 (median 31 days; p = 0.0001), in the OncoGel 6.3 group on Day 5 (median 17 days; p = 0.02), and in the radiation therapy-only group (median 26 days; p = 0.0001) compared with controls. Animals receiving both OncoGel and radiation therapy had the longest median survival: 83 days in the group with radiation therapy combined with OncoGel 6.3 on Day 0, and 32 days in the group combined with OncoGel 6.3 on Day 5 (p = 0.0001 vs controls). After 120 days, 37.5% of the animals in the OncoGel Day 0 group, 37.5% of animals in the OncoGel 6.3 Day 0 in combination with radiation therapy group, and 12.5% of the animals in the OncoGel 6.3 on Day 5 in combination with radiation therapy group were alive. In the biodistribution study, measurable radioactivity was observed throughout the ipsilateral hemisphere up to 3 weeks after the OncoGel injection, with the most radioactivity detected 3 hours after injection. The highest dose of radioactivity observed in the contralateral hemisphere was at the Day 3 time point. CONCLUSIONS: OncoGel containing 6.3 mg/ml of paclitaxel is safe for intracranial injection in rats and effective when administered on Day 0. When combined with radiation therapy, the combination was more effective than either therapy alone and should be studied clinically for the treatment of malignant glioma.

Massive venous air embolism in the semi-sitting position during surgery for a cervical spinal cord tumor: anatomic and surgical pitfalls.

Although venous air embolism (VAE) in neurological surgery is mainly associated with posterior fossa procedures, this complication may also occur, with comparable severity, in the posterior cervical spine approach in patients who are semi-sitting. We report a patient with a massive VAE that occurred in the semi-sitting position during a posterior approach to an extended cervical-thoracic level (C3-T2) intramedullary tumor, which interrupted the surgical procedure. We discuss the possible causes of air embolism, the anatomic and pathogenetic mechanisms, treatment and preventive measures.

Atypical cystic meningioma overexpressing AQP1 in early infancy: case report with literature review.

UNLABELLED: Meningiomas in early infancy are rare lesions, worth to be reported for their exceptional occurrence. The authors report a case of an 11-month-old female child with asymmetric macrocephaly due to the presence of a cystic atypical meningioma associated to bilateral subdural collections. CONCLUSION: This unusual and unique case of atypical cystic meningioma in early infancy showed a high positivity to immunostaining of aquaporin 1, and this pattern could correlate with the coexistence both of cysts and subdural collections.

Causes of arachnoid cyst development and expansion.

Arachnoid cysts are frequent incidental findings on neuroimaging studies and in clinical practice. Theories of their origin, still matter for debate, compose four categories: 1) a ball-valve mechanism; 2) an osmotic gradient between the intra- and extracystic medium; 3) primary malformation of the arachnoid membrane or cerebral lobe agenesis; and 4) fluid hypersecretion by the lining cells of the cyst wall. The cause of cyst enlargement is also debatable, although there is strong controversial evidence supporting the last two theories rather than the former. Brain water homeostasis and its regulatory pathways are weakly understood at the molecular level. In this brief report the authors attempt to add new insights into the pathogenesis of arachnoid cysts by considering aquaporin expression in the cyst wall and discuss possible future research directions and molecular targets.

Aquaporin(s) expression in choroid plexus tumours.

OBJECTIVE: It was the aim of this study to investigate the pattern of aquaporin 1 (AQP1) expression in normal and neoplastic choroid plexus, with specific reference to the association with communicating hydrocephalus or liquoral cysts. Second, to infer a new view on the cerebrospinal fluid plexus production and on the etiology of the cysts and communicating hydrocephalus occasionally associated with choroid plexus papillomas. MATERIALS AND METHODS: Nineteen paraffin-embedded specimens, 10 of normal choroid plexus and 9 of choroid plexus tumours, were immunostained with a monoclonal antibody raised against the intracellular C-terminal AQP1 epitope. Results were analysed in terms of intensity and intracellular distribution of immunostaining and in terms of number of stained cells; they were considered in light of the clinical association with hydrocephalus or liquoral cysts. RESULTS: AQP1 was heavily expressed in the apical side of the choroid epithelium in normal plexus specimens. Choroid plexus papillomas showed a very heterogeneous pattern of AQP1 expression. Immunostaining was absent in the case of choroid plexus carcinoma. Very strong to strong and diffuse AQP1 expression in large to very large papillomas was associated with liquoral cysts or communicating hydrocephalus. CONCLUSIONS: AQP1 expression characterizes normal choroid plexus and plexus papillomas. Intensity and diffusion of AQP1 expression together with the size of the tumour mass are somewhat predictive of communicating hydrocephalus or liquoral cyst, lesions possibly caused by a disturbance of cerebrospinal fluid homeostasis.