Fluorescein-assisted stereotactic needle biopsy of brain tumors: a single-center experience and systematic review.

Over the last years, fluorescence-based technology has begun an emergent intraoperative method for diagnostic confirmation of brain tumor tissue in stereotactic needle biopsy. However, the actual level of evidence is quite low, especially about fluorescein sodium (FL) application. This method needs to be further validated and better analyzed about its impact in clinical practice. Retrospective analysis of 11 cases with contrast-enhancing brain tumors, underwent awake stereotactic needle biopsy with intraoperative FL assistance (group 1), was verified under the operative microscope filter. This group was matched with a control group of 18 patients (group 2). In addition, a systematic literature review was performed in PubMed/Medline database according to PRISMA statement. All studies concerning FL or 5-ALA application in stereotactic biopsy as intraoperative confirmation of brain tumor tissue were included. The primary endpoint was the evaluation of diagnostic accuracy. In group 1, all fluorescent specimens were diagnostic. The number of samplings was the useful minimum and non-use of intraoperative neuropathological examination allowed to significantly reduce procedure time (42.09 vs 69.72 min of group 2). No complications occurred, and the average hospitalization time after procedure was 1.09 days (vs 2.33 of group 2). Literature analysis supports the usefulness of photodiagnosis and its high diagnostic yield especially at the core of high-grade/contrast-enhancing tumors. FL assistance during stereotactic biopsy of contrast-enhancing brain tumors may give a real-time confirmation of tumor tissue, maximizing the diagnostic yield, and reducing time of procedure, morbidity, and hospitalization.

Cerebrovascular disorders and Fahr's disease: Report of two cases and literature review.

Fahr's disease is a rare idiopathic nosological entity, characterized by calcification of the basal ganglia and dentate nuclei of the cerebellum. Sometimes it may be associated to other diseases like cerebrovascular disorders. However, this link remains unclear and it needs to be further validated. We report two cases of patients with cerebrovascular disorders and Fahr's disease. In the first case, a 69-years-old woman with right internal capsule-basal ganglia haemorrhage. In the second case, a 72-years-old woman with ischemic stroke and pericallosal artery aneurysm. The physiopathology is discussed and concerning literature is reviewed.

Deregulated expression and activity of Farnesyl Diphosphate Synthase (FDPS) in Glioblastoma.

Glioblastoma (GBM), the most aggressive brain cancer, is highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical for cell proliferation but the function and regulation of key intermediate enzymes like farnesyl-diphosphate synthase (FDPS), up to now, remained unknown. A deregulated expression and activity of FDPS was the central research idea of the present study. FDPS mRNA, protein and enzyme activity were analyzed in a cohort of stage III-IV glioma patients (N = 49) and primary derived cells. FDPS silencing helped to clarify its function in the maintenance of malignant phenotype. Interestingly, compared to tumor-free peripheral (TFB) brain and normal human astrocytes (NHA), FDPS protein expression and enzyme activity were detected at high degree in tumor mass where a correlation with canonical oncogenic signaling pathways such as STAT3, ERK and AKT was also documented. Further, FDPS knockdown in U87 and GBM primary cells but not in NHA, enhanced apoptosis. With the effort to develop a more refined map of the connectivity between signal transduction pathways and metabolic networks in cancer FDPS as a new candidate metabolic oncogene in glioblastoma, might suggest to further target MVA pathway as valid therapeutic tool.

Fluorescein-Guided Surgery for High-Grade Glioma Resection: An Intraoperative "Contrast-Enhancer".

BACKGROUND: Fluorescein sodium salt is widely used in medicine as fluorescein isothiocyanate and commonly named fluorescein (FL). This fluorophore has been used as a fluorescent tracer for many applications, especially in ophthalmic surgery. It was initially used in neuro-oncology in 1948 to control tumor resection margins. After a transient disuse, it has recently had a second spring with the development of dedicated filters for operating microscopes, although it is still under evaluation in clinical use. The aim of this study is to contribute to the investigation according to which FL-guided surgery for high-grade glioma (HGG) is related to better rates of gross total resection (GTR) and so to a better outcome. METHODS: We retrospectively analyzed 23 cases of patients with new diagnosis of HGG, operated on in our unit by intraoperative FL use with a filter system directly integrated into an operative microscope (group 1). Fluorescence was compared with histology by biopsies carried out both in the fluorescent areas and in the periphery of fluorescent areas. Group 1 was matched with a control group of 25 patients with HGG operated on in our unit during the last 2 years without FL guidance (group 2). RESULTS: No side effects occurred related to FL. Histology and intraoperative neuronavigation showed strong correspondence with fluorescent and nonfluorescent areas. GTR rate was significantly higher in group 1 (82.6%) than in group 2 (52%). CONCLUSIONS: Intraoperative fluorescein-guided surgery showed safety and feasibility. Our and other studies suggest an improvement of GTR rate in HGG than nonuse.

Antiglioma effects of N6-isopentenyladenosine, an endogenous isoprenoid end product, through the downregulation of epidermal growth factor receptor.

Malignant gliomas are highly dependent on the isoprenoid pathway for the synthesis of lipid moieties critical for cell proliferation. The isoprenoid derivative N6-isopentenyladenosine (iPA) displays pleiotropic biological effects, including a direct anti-tumor activity in several tumor models. The antiglioma effects of iPA was then explored in U87MG cells both in vitro and grafted in mice and the related molecular mechanism confirmed in primary derived patients' glioma cells. iPA powerfully inhibited tumor cell growth and induced caspase-dependent apoptosis through a mechanism involving a marked accumulation of the pro-apoptotic BIM protein and inhibition of EGFR. Indeed, activating AMPK following conversion into its iPAMP active form, iPA stimulated EGFR phosphorylation and ubiquitination along a proteasome-mediated pathway which was responsible for receptor degradation and its downstream signaling pathways inhibition, including the STAT3, ERK and AKT cascade. The inhibition of AMPK by compound C prevented iPA-mediated phosphorylation of EGFR, known to precede receptor loss. As expected the block of EGFR degradation, by exposure to the proteasome inhibitor MG132, significantly reduced iPA-induced cell death. Given the importance of receptor degradation in iPA-mediated cytotoxicity, we also documented that the EGFR expression levels in a panel of primary glioma cells confers them a high sensitivity to iPA treatment. In conclusion our study provides the first evidence of iPA antiglioma effect. Indeed, as glioma is driven by aberrant signaling of growth factor receptors, particularly the EGFR, iPA, alone or in association with EGFR targeted therapies, might be a promising therapeutic tool to achieve a potent anti-tumoral effect.

The use of a three-dimensional endoscope for different skull base tumors: results of a preliminary extended endonasal surgical series.

BACKGROUND: The evolution of skull base surgery over the past decade has been influenced by advancement in visualization technology. Recently, as a result of such improvements, three-dimensional (3-D) scopes have been widely used during endoscopic endonasal approaches. In the present study, we describe the use of 3-D stereoscopic endoscope for the treatment of a variety of skull base lesions. METHODS: From January 2010 to June 2015, a 3-D endoscopic endonasal approach (4 and 4.9 mm, 0°, and 30° rigid endoscopes) was performed in 70 patients with the following lesions: 42 large extrasellar pituitary macroadenomas, seven tuberculum sellae meningiomas, seven clivus chordomas, five craniopharyngiomas, three fibrous dysplasia of the clivus, three sinonasal malignancies, one orbital lymphangioma, one trigeminal neurinoma, one primary suprasellar lymphoma. RESULTS: Total tumor removal was obtained in 50 patients (71.4 %) while in 14 (20 %), subtotal removal was possible in six (8.6 %) only partial removal was achieved. Overall complications included diabetes insipidus in eight patients (11.4 %), hypopituitarism in seven patients (10 %), CSF leak in five patients (7.1 %), cranial nerve injury in two patients (2.8 %), panhypopituitarism in two patients (2.8 %), meningitis in one (1.4 %) and one postoperative central retinal artery occlusion (1.4 %). There was no mortality in the series. The mean follow-up time was 39 months (range, 6-72 months). CONCLUSIONS: In our experience, the 3-D endoscope represents a critical development in visualization, thus enabling improved hand-eye coordination and depth perception, which are mandatory for the management of complex intradural neurovascular structures during tumor removal surgery.

Treatment of Chiari malformation: who, when and how.

There is no effective alternative to surgery in the treatment of the symptomatic cases of chiari malformation. Nonetheless, in literature there is no unanimous consensus about what is the surgical "gold standard" and which are the candidates for surgery. No doubt that intracranial hypertension and ventricular dilatation have to be investigated and treated before considering decompression. It is also very important to keep in mind that a surgery does not guarantee a complete recovery from every symptoms. We report our experience about who are the candidates for surgery, which is the most appropriate surgical technique and when is the correct time for surgery along the natural history of the disease.

Endoscopy versus microsurgical cyst excision and shunting for treating intracranial arachnoid cysts.

OBJECT: Endoscopic surgery is routinely used to treat intracranial arachnoid cysts. However, the indications and results with respect to the different cyst locations, compared with those of microsurgical fenestration and cyst shunting, deserve to be discussed. METHODS: The authors review 18 patients with intracranial arachnoid cysts treated by pure endoscopic technique in their neurosurgical department. There were 10 male and 8 female patients ranging in age from 2 months to 48 years (median age 19.4 years). The cyst location was suprasellar in 5 cases, quadrigeminal in 5, cortical hemispheric in 2, sylvian region in 3, and posterior fossa in 3. The authors also reviewed the literature, comprising 61 reports for an overall number of 645 patients with intracranial arachnoid cysts treated by different surgical techniques. These techniques included microsurgical excision or fenestration by craniotomy, cyst shunting, and endoscopic fenestration. The surgical results of the different techniques according to the different cyst locations underwent statistical analysis. RESULTS: The overall success rate (complete or partial clinical remission) in the authors' endoscopic series was 83.3% (15 of 18 cases), which is rather similar to that of 222 patients treated endoscopically and reported on in the literature (84.2%). In the overall endoscopic group, a higher success rate was found for cysts in the suprasellar (89.7%), quadrigeminal (88.5%), and posterior cranial fossa (83.3%) regions compared with sylvian (70%) and cortical and interhemispheric (75%) regions. The statistical comparison of the results of the endoscopic series with those of craniotomy and shunting revealed no significant differences for suprasellar, quadrigeminal, or posterior cranial fossa cysts, whereas the success rate of endoscopy is lower than that of other techniques for sylvian and cortical cysts. CONCLUSIONS: Endoscopy is a safe and effective therapeutic modality for patients with intracranial arachnoid cysts. Cysts of the suprasellar and quadrigeminal regions and posterior fossa are the best indications for neuroendoscopy; on the other hand, cortical cysts are best treated by microsurgical fenestration or shunting. For sylvian cysts, the endoscopic procedure may be advocated in most cases.

Recurrent acute obstructive hydrocephalus as clinical onset of cerebral Whipple's disease.

Whipple's disease is a rare multisystemic infection caused by the intracellular bacteria Thropheryma whippelii. Central nervous system (CNS) involvement is not rare. The most frequent CNS manifestations are cognitive and behavioural changes, sopranuclear ophtalmoplegia, myoclonus, epilepsy, ataxia, meningitis and focal cerebral palsy. We report one case of cerebral localization of Whipple's disease with a clinical presentation of recurrent endocranic hypertension and hydrocephalus, and uncommon neurological symptoms, successfully treated by endoscopic third ventriculostomy and antibiotic therapy with ceftriaxone and Trimethoprim-Sulfamethoxazole.

Combined endoscopic and microsurgical removal of a giant cystic craniopharyngioma in a six-year-old boy.

Giant cystic craniopharyngiomas are rare lesions whose clinical and surgical management is extremely challenging, often requiring more than one craniotomy before obtaining a satisfying removal. We report one case of a giant cystic craniopharyngioma completely excised with a two-step combined use of a minimally invasive endoscopic approach followed by a single microsurgical transcranial procedure. A six-year-old boy presented with symptoms of increased intracranial pressure and posterior fossa involvement. Preliminary imaging revealed a large para- and suprasellar cystic tumor bulging superiorly into the third ventricle, and extending posteriorly from the retroclival region into the posterior fossa to the level of the foramen magnum. The suprasellar cystic quota was initially approached endoscopically through a right precoronal-transventricular approach and the cyst drained, while the remaining tumor was macroscopically totally removed one week later by a right pterional approach. A combined technique--endoscopic drainage followed by microsurgical removal--can be a valid alternative for the removal of giant cystic craniopharyngiomas in cases in which the cystic compartment bulges within the ventricular spaces, and may avoid multiple craniotomies.