Transaqueductal navigation of the fourth ventricle has long been considered dangerous and of no clinical relevance. After the refinement of the endoscopic technique and supported by the extensive experience gained at the authors' institution since 1994, endoscopic exploration of the fourth ventricle has been performed by the same surgeon in 54 patients. In all cases reviewed, endoscopic navigation of the fourth ventricle was successfully performed with no related neurological deficit. This preliminary experience shows the feasibility of transaqueductal navigation of the fourth ventricle, which is made possible by the use of small, flexible endoscopes in expert hands.
Technical note and preliminary experience
Pierluigi Longatti, Luca Basaldella, Alberto Feletti, Alessandro Fiorindi and Domenico Billeci
Luca Basaldella, Elisabetta Marton, Alessandro Fiorindi, Bruno Scarpa, Hadi Badreddine and Pierluigi Longatti
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.
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.
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.
The reduction in internal shunt surgery encourages the adoption of neuroendoscopic aspiration of severe IVH as a therapeutic tool to decrease shunt dependency.
Pierluigi Longatti, Andrea Porzionato, Luca Basaldella, Alessandro Fiorindi, Pietro De Caro and Alberto Feletti
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.
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.
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.
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.
Pierluigi Longatti, Alessandro Fiorindi, Paolo Peruzzo, Luca Basaldella and Francesca Maria Susin
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.
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.
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.
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.
Luca Basaldella, Enrico Orvieto, Angelo Paolo Dei Tos, Mila Della Barbera, Marialuisa Valente and Pierluigi Longatti
✓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.
Betty Tyler, Kirk D. Fowers, Khan W. Li, Violette Renard Recinos, Justin M. Caplan, Alia Hdeib, Rachel Grossman, Luca Basaldella, Kimon Bekelis, Gustavo Pradilla, Federico Legnani and Henry Brem
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.
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.
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.
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.