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ENDOSCOPIC TRANSORAL-TRANSCLIVAL APPROACH TO THE BRAINSTEM AND SURROUNDING CISTERNAL SPACE: ANATOMIC STUDY

OBJECTIVEThe purpose of this study was to review the endoscopic anatomic features of the anterior brainstem and surrounding cisternal spaces via a transoral-transclival approach. METHODSFifteen adult human cadaveric heads, obtained from 10 fresh cadavers and 5 formalin-fixed cadavers, were used to demonstrate both the feasibility of an endoscopic transoral-transclival intradural approach and its exposure potential. To analyze the exact extension of a safe entry zone through the clivus, 20 skull bases were used to obtain anatomic measurements. RESULTSThe transoral approach was performed without maxillotomy or mandibulotomy and with a clival opening of 20 by 15 mm. Such a limited clival and dural opening allowed the insertion of the endoscope and instruments, full visualization of the anterolateral brainstem and cisternal spaces around it, and reconstruction of all anatomic layers by means of a paraendoscopic technique. CONCLUSIONThe endoscopic transoral-transclival approach enables full access to the anterolateral brainstem and to the cisternal space around it. The use of the endoscope has the potential to reduce the need for a wider cranial base opening and the danger of postoperative complications.

Microsurgical anatomic features of the lamina terminalis.

OBJECTIVE The lamina terminalis (LT) is a structure of considerable interest for microneurosurgery, and precise knowledge regarding its normal anatomic features and the variations thereof is required. The purpose of this study, which was based on microanatomic dissection of human cadaveric specimens, was to review the microsurgical anatomic features of the LT and its neurovascular relationships. The surgical implications of the morphometric data are discussed. METHODS The region of the LT was examined in 10 human cadaveric heads, obtained from 8 fresh adult cadavers and 2 formalin-fixed adult cadavers, and in 10 formalin-fixed, isolated, adult brains. An operating microscope was used for all dissections and measurements. RESULTS Assuming the LT to be a triangular structure, we performed measurements of the distance between the midportion of the upper edge of the chiasm and the lower edge of the anterior commissure (height), which averaged 8.25 mm. The distance between the medial edges of the optic tracts (base) averaged 12.81 mm. The area averaged 52.84 mm2. A minimal amount of retraction was needed to fully expose the LT, and generally there was no need to mobilize the anterior cerebral artery-anterior communicating artery complex. Perforating branches to the hypothalamus and optic apparatus are laterally located and do not interfere with LT incision and/or fenestration. CONCLUSION The LT constitutes a clearly identifiable microsurgical target. The allowable extent of LT opening is sufficient to provide wide access into and free cerebrospinal fluid flow from the third ventricle. Fenestration of the LT is a safe procedure, provided that the relevant anatomic landmarks are identified and respected.

Radiation-Induced Blood-Brain Barrier Changes: Pathophysiological Mechanisms and Clinical Implications

The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

Anterior skull base reconstruction with a galeal-pericranial flap.

Excision of neoplasm and trauma involving the anterior cranial base may often result in communication between the intracranial and extracranial compartments. Many techniques have been proposed to obtain a watertight separation. We report our 5 years of experience in the management of anterior skull base defects using a galeal-pericranial flap. Between January 2001 and April 2006, 22 patients were treated for a cranial base reconstruction at the University of Messina. Five of them presented with persistent cerebrospinal fluid (CSF) leak after previous craniofacial trauma. Ten underwent a combined maxillofacial-neurosurgical approach for the removal of a benign tumor involving the anterior skull base. Seven had severe craniofacial trauma, which required an intervention of reconstruction of the anterior skull base. In the whole series, a galeal-pericranial flap was used to separate intra- and extracranial compartments. No patients developed postoperative brain contusions or subdural-epidural blood collections. Throughout the follow-up period, there was no evidence of flap failure. In all but one patient, no postoperative CSF leak was evident. In one patient, a mild transient postoperative CSF leakage was present. There has been no recurrent CSF leak or meningitis. The follow up average of 23 months shows no incidence of infection. Even if our series does not comprise malignancies and previously irradiated patients, our data confirm the validity of the galeal- pericranial flap for the surgical management of minimal and moderately sized defects of anterior cranial base.

Large sphenocavernous meningiomas: Is there still a role for the intradural approach via the pterional-transsylvian route?

Summary. Background: Large-sized sphenocavernous meningiomas represent a surgical challenge. Although the role of skull base techniques with combined extra- and intradural steps has been recently emphasized, pure intradural resection tactics via the pterional route constitute the traditional microsurgical approach for resection of such tumours. Method: We report the application of the pterional-transsylvian approach in 13 patients with sphenocavernous meningiomas. This series is unique because it includes only patients with tumours exceeding 5 cm in their greatest dimension. Findings: A gross total resection was accomplished in 10 patients (77%). Eight patients had a good outcome, one had a persistent mild hemiparesis, and one died. No recurrences occurred in this group. Three patients (23%) had subtotal resections owing to invasion of the cavernous sinus in one instance and encasement of the middle cerebral artery in the others. Two had a good outcome and one died. In these patients minimal asymptomatic tumour progression was seen 3 and 6 years after surgery. The overall surgical outcome was good in 10 patients (77%), fair in one, and death in two. Interpretation: In our experience, large sphenocavernous meningiomas may be operated on adopting pure intradural resection tactics via the pterional-transsylvian route with rates of gross total removal and surgical complications related to brain retraction or vascular manipulation comparable to those of extensive skull base approaches. The traditional intradural pterional transsylvian approach continues to have a place in the treatment of these lesions.

Expression of telomeric repeat binding factor-1 in astroglial brain tumors.

OBJECTIVE:In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS:Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS:TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P = 0.0032). TRF1 expression correlated with the patient’s length of survival (P < 0.001) and performance status (P < 0.001) and proved to be an independent indicator of length of survival. CONCLUSION:Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors.

Extended endoscopic endonasal transclival approach to the ventrolateral brainstem and related cisternal spaces: anatomical study

Advances in endoscopic endonasal skull base surgery have led to the development of new routes to areas beyond the midline skull base. Recently, feasible surgical corridors to the lateral skull base have been described. The aim of this study was to describe the anatomical exposure of the ventrolateral brainstem and posterior fossa through an extended endoscopic endonasal transclival transpetrosal and transcondylar approach. Six human heads were used for the dissection process. The arterial and venous systems were injected with red- and blue-colored latex, respectively. A pre- and postoperative computed tomography (CT) scan was carried out on every head. The endoscopic endonasal transclival approach was extended through an anterior petrosectomy and a medial condylectomy. A three-dimensional model of the approach was reconstructed, using a dedicated software, from the overlapping of the pre- and post-dissection CT imaging of the specimen. An extended endoscopic transclival approach allows to gain access through an extradural anterior petrosectomy and medial condylectomy to the anterolateral surface of the brainstem and the posterior fossa. Two main intradural anatomical corridors can be described: first, between the V cranial nerve in the prepontine cistern and the VII–VIII cranial nerves in the cerebellopontine and cerebellomedullary cistern; second, between the VII–VIII cranial nerves and the IX cranial nerve, in the premedullary cistern. Extending the transclival endoscopic approach by performing an extradural anterior petrosectomy and a medial condylectomy provides a safe and wide exposure of the anterolateral brainstem with feasible surgical corridors around the main neurovascular structures.

Silencing of telomere-binding protein adrenocortical dysplasia (ACD) homolog enhances radiosensitivity in glioblastoma cells

&NA; Adrenocortical dysplasia (ACD) is a shelterin protein involved in the maintenance of telomere length and in cancer radioresistance. This study investigated the expression profile of ACD in human gliomas and its role in radioresistance of glioma cells. The expression of ACD was analyzed in 62 different grades of glioma tissues and correlated with prognosis. A radioresistant cell line was generated from U87MG cells. For mechanistic studies, ACD was inhibited by small interfering RNA‐targeting ACD and the effect on cell radioresistance, telomerase activity, cyclinD1, caspase‐3, hTERT, and BIRC1 was evaluated. Clonogenic assay was performed after irradiation, to investigate the effect of ACD silencing on radiation sensitivity. ACD expression appeared strongly upregulated in higher grade gliomas, and its expression was significantly correlated to grading and poor prognosis. In glioma cell lines, ACD expression pattern was similar to those observed in glioma tissues. In irradiated cells, ACD expression was increased in an ionizing radiation dose‐dependent manner. A higher expression of ACD was observed in the radioresistant clones than parental cells. Silencing of ACD led to the enhanced radiation sensitivity, decreased telomerase activity and cyclin D1 expression, reduced expression of BIRC1, and finally to the upregulation of caspase‐3. This study represents the first report, which demonstrated the expression pattern of ACD in gliomas and its prognostic value. Our results suggested that ACD is involved in glioblastoma radioresistance, likely through the modulation of telomerase activity, proliferation, and apoptosis. ACD might represent a potential molecular biomarker and a novel therapeutic target in glioblastoma.

L’apoplessia ipofisaria: riconoscerla rapidamente e trattarla correttamente

SommarioL’apoplessia ipofisaria rappresenta un’emergenza medico-chirurgica la cui gestione compete a un esperto team multidisciplinare composto da endocrinologi, radiologi, oculisti e neurochirurghi. Una tempestiva diagnosi e un’adeguata valutazione delle conseguenze neuro-oftalmologiche e endocrinologiche sono essenziali per l’adozione di interventi terapeutici equilibrati ed efficaci, finalizzati primariamente alla salvaguardia delle capacità visive. Il rischio di ipopituitarismo è elevato e l’iposurrenalismo in particolare svolge un ruolo cruciale sul decorso clinico.