Parietal interhemispheric transfalcine transtentorial approach for posterior incisural space lesions: from the lab to the operative room.

The operative approach to the posterior incisural space is challenging because of its deep location, the surrounding eloquent areas, and the intimate relationship with the deep veins. Several approaches have been proposed to manage the lesions in this region: supratentorial, infratentorial and a combination of them. Brain retraction, injury to the occipital lobe and corpus callosum, and venous bleeding are the principle drawbacks of these routes. We performed anatomical dissection study using 10 embalmed human cadaver specimens injected with colored latex exploring a different route, parietal interhemispheric transfalcine transtentorial (PITT). Then we used a PITT approach on two patients with posterior incisural space (PIS) lesions. The PITT approach led to successful and safe complete removal of PIS lesions in our cases. No complications were reported. The present approach could be a valuable option in case of PIS lesions, especially those associated with downward displacement of the deep venous complex; thanks to the gravity it reduce the complications related to the occipital lobe retraction and manipulation. Moreover, cutting the superior-anterior edge of the tentorium, the sub-tentorial space could be reached.

Metastatic squamous cell carcinoma to the brain: an unrecognized pattern of distant spread in patients with HPV-related head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is notorious for local recurrence and metastatic spread to regional lymph nodes. Distant spread is uncommon, and brain involvement is rare. Over the past decade there has been a rising incidence of HPV-related HNSCC, but it is not known if this escalation has had any impact on trends relating to brain involvement. Cases of metastatic squamous cell carcinoma (SCC) to the brain were identified from a computerized search of the surgical pathology files of The Johns Hopkins Hospital between 1985 and 2012. The medical records were reviewed to document primary site of tumor origin, treatment, and patient outcome. P16 immunohistochemistry and HPV in situ hybridization were performed on those metastases arising from the head and neck. Of the 38 metastatic SCCs, 7 (18 %) originated in the head and neck. HPV-16 was detected in 4 (57 %) of the metastatic HNSCCs. All 4 HPV-positive metastases were from oropharyngeal primaries. The time from treatment of the primary to development of the brain metastasis ranged from 19 to 57 months (mean, 45). Following aggressive treatment (surgery and radiation), two patients died of disease progression (7 and 34 months), and two are alive with recurrent brain metastases (4 and 10 months). Although HPV positivity is regarded as a favorable prognostic indicator, it does not safeguard from spread to the brain. In our experience, just over half of the HNSCCs that metastasized to the brain were HPV-related. The potential for developing a brain metastasis long after curative therapy argues for extended patient follow-up. The development of a brain metastasis is an ominous finding signaling rapid clinical deterioration.

MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.

Transformed, oncogenic precursors, possessing both defining neural-stem-cell properties and the ability to initiate intracerebral tumours, have been identified in human brain cancers. Here we report that bone morphogenetic proteins (BMPs), amongst which BMP4 elicits the strongest effect, trigger a significant reduction in the stem-like, tumour-initiating precursors of human glioblastomas (GBMs). Transient in vitro exposure to BMP4 abolishes the capacity of transplanted GBM cells to establish intracerebral GBMs. Most importantly, in vivo delivery of BMP4 effectively blocks the tumour growth and associated mortality that occur in 100% of mice after intracerebral grafting of human GBM cells. We demonstrate that BMPs activate their cognate receptors (BMPRs) and trigger the Smad signalling cascade in cells isolated from human glioblastomas (GBMs). This is followed by a reduction in proliferation, and increased expression of markers of neural differentiation, with no effect on cell viability. The concomitant reduction in clonogenic ability, in the size of the CD133+ population and in the growth kinetics of GBM cells indicates that BMP4 reduces the tumour-initiating cell pool of GBMs. These findings show that the BMP-BMPR signalling system--which controls the activity of normal brain stem cells--may also act as a key inhibitory regulator of tumour-initiating, stem-like cells from GBMs and the results also identify BMP4 as a novel, non-cytotoxic therapeutic effector, which may be used to prevent growth and recurrence of GBMs in humans.

The supraorbital craniotomy for access to the skull base and intraaxial lesions: a technique in evolution.

INTRODUCTION: The supraorbital craniotomy was initially described as a minimally invasive means to target extra-axial lesions in the anterior cranial fossa and sellar/parasellar region. Since its initial description, various modifications have been described. We report our recent experience with this approach (and its modifications) for not only extra-axial but also intra-axial neoplastic pathology. METHODS: Based on patient pathology and anatomic considerations, one of two approaches was performed: supraorbital craniotomy through an eyebrow incision or a combined orbital osteotomy and supraorbital craniotomy through an eyelid incision. RESULTS: This technique was performed on twenty-eight consecutive patients. Intra-axial pathology ranged from anaplastic astrocytoma to metastasis while extra-axial lesions included meningiomas and skull-based metastases. Excellent lesion resection was achieved in the majority of patients. Complications were infection (2 patients) and CSF leak. DISCUSSION: The supraorbital craniotomy and its modifications provide an ideal anterior subfrontal approach through which a wide variety of pathology can be approached. This technique has particular considerations in comparison to traditional cranial base approaches that must be taken into account before it is utilized.

Preliminary experience with 4K ultra-high definition endoscope: analysis of pros and cons in skull base surgery.

During the last two decades endoscopic skull base surgery observed a continuous technical and technological development 3D endoscopy and ultra High Definition (HD) endoscopy have provided great advances in terms of visualisation and spatial resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the clinical practice, will shape next steps forward especially in skull base surgery field. Patients were operated on through transnasal transsphenoidal endoscopic approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0° Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging (NBI) technology connected through a camera head to a high-quality control unit (OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan). Two screens are used, one 31" Monitor - (LMD-X310S) and one main ultra-HD 55" screen optimised for UHD image reproduction (LMD-X550S). In selected cases, we used a navigation system (Stealthstation S7, Medtronic, Minneapolis, MN, US). We evaluated 22 pituitary adenomas (86.3% macroadenomas; 13.7% microadenomas). 50% were not functional (NF), 22.8% GH, 18.2% ACTH, 9% PRL-secreting. Three of 22 were recurrences. In 91% of cases we achieved total removal, while in 9% near total resection. A mean follow-up of 187 days and average length of hospitalisation was 3.09 ± 0.61 days. Surgical duration was 128.18± 30.74 minutes. We experienced only 1 case of intraoperative low flow fistula with no further complications. None of the cases required any post- or intraoperative blood transfusion. The visualisation and high resolution of the operative field provided a very detailed view of all anatomical structures and pathologies allowing an improvement in safety and efficacy of the surgical procedure. The operative time was similar to the standard 2D HD and 3D procedures and the physical strain was also comparable to others in terms of ergonomics and weight.

Trichophyton concentricum in skin lesions in children from the Salomon Islands.

AIM: Aim of the paper was to report cases of Tinea imbricata, a mycosis caused by the anthropophilic dermatophyte Trichophyton concentricum, observed in 2012 in Guadalcanal, the largest of the Salomon islands. METHODS: During 2012, several cases of Tinea imbricata, called bakwa by local people, were observed in the Little Samaritan Hospital in Guadalcanal. Skin scrapings collected from three young patients were examined in Italy to confirm the clinical diagnosis. The fungus grown on culture was morphologically identified and submitted to sequencing of the ITS1-ITS2 region. RESULTS: The diagnosis obtained by visual inspection of the skin lesions, characterised by concentric and lamellar plaques of scale often involving large part of the body, was confirmed mycological investigations. A prevalence of 15% of Tinea imbricata in this population was hypothesized. The fungus grown on culture was morphologically identified as Trichophyton concentricum and identification was confirmed sequencing the ITS1-ITS2 region. Patients were treated with potassium permanganate solution soaked gauze followed by colloidal sulfur and salicylic acid cream application. However, the efficacy of the antifungal treatment was difficult to evaluate due to the poor compliance of the patients and the remoteness of the villages. CONCLUSION: Italian clinicians and mycologists should be aware of this fungal infection because the increased number of international travels and of migration rise the spread of infections previously restricted to limited geographical areas.

Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia.

Sensitive methods are required to record electrical evoked potentials over the visual cortex to evaluate the efficacy and safety of a retinal prosthesis before it can be implanted on the retinal surface of patients afflicted by outer retinal diseases. This study was designed to examine subdural electrodes as a mean to evaluate cortical evoked potentials in response to light and electrical stimulation of the retina in three dogs under two methods of anesthesia-halothane and propofol. Results showed that subdural electrodes could be stabilized over the visual cortex for several (3-5) months, and that they were 6.95 times more sensitive than subdermal electrodes in recording cortical visual evoked potentials (VEPs) and 4.31 times more sensitive in recording cortical electrical evoked potentials under both methods of anesthesia. The waveforms' shape changed for each electrode in the subdural array during 6/6 (100%) and 20/38 (52%) multi-channel recording sessions under halothane and propofol, respectively. This change could point to a cortical retinotopic organization versus hierarchical organization of different cortical areas for a given retinal stimulus. In summary, subdural electrodes show promising results for recording visual and electrical evoked responses (EERs) and thus for evaluation of the retinal prosthesis.

Direct delivery of platinum-based antineoplastics to the central nervous system: a toxicity and ultrastructural study.

Platinum drugs are playing an increasingly major role in cancer treatment, but systemic administration of these agents has resulted in significant toxicity. To examine the effects of cisplatin and two newer agents, iproplatin and carboplatin, we injected the agents directly into the cerebrospinal fluid of rats and found that neurotoxic reactions resulted from doses of cisplatin (10 nmol) much lower than those of iproplatin (40 nmol) or carboplatin (80 nmol). Moreover, central nervous system tissue appeared to be less adversely affected by direct exposure to carboplatin since chronic toxicity was not observed in any of the animals receiving carboplatin until a lethal dose was reached. Furthermore, only the animals receiving cisplatin showed histologic damage in their spinal cords, and ultrastructural studies confirmed that while significant abnormalities were observed in the spinal cords of rats receiving 40 nmol cisplatin, no architectural changes were detected in the spinal cords of animals receiving 240 nmol carboplatin. We conclude that platinum drugs can be delivered intrathecally to achieve a much greater concentration of active drug than can be achieved by intravenous administration and that carboplatin appears to be the most suitable platinum-based drug for use in systems delivering drugs directly to the brain and spinal cord.

Interstitial delivery of carboplatin via biodegradable polymers is effective against experimental glioma in the rat.

PURPOSE: Carboplatin has shown promise experimentally as an antineoplastic agent against both primary central nervous system (CNS) tumors and several solid tumors that frequently metastasize to the brain. Unfortunately, carboplatin is limited in its clinical use for tumors in the CNS by systemic toxicity and poor penetration through the blood brain barrier. Recent advances in polymer technology have made feasible the intracranial implantation of a biodegradable polymer capable of local sustained delivery of chemotherapy for brain neoplasms. This study assessed the toxicity and efficacy of carboplatin delivered from intracranial sustained release polymers in the treatment of experimental gliomas in rodents. METHODS: Two biodegradable anhydride polymer systems were tested: a copolymer of 1,3-bis-(p-carboxyphenoxy propane) and sebacic acid, and a copolymer of fatty acid dimer and sebacic acid. The polymers were loaded with carboplatin and dose escalation studies evaluating toxicity were performed by implanting carboplatin-loaded polymers into the brains of rats. Next, efficacy was tested. F-98 glioma cells were injected intracranially into rats, and 5 days later polymers containing the highest tolerated doses were implanted at the site of tumor growth. The survival of animals receiving carboplatin-loaded polymer was compared with that of animals receiving intraperitoneal doses of the same agent. RESULTS: Carboplatin-polymer was well tolerated at doses up to 5% loading in both polymer systems. Locally delivered carboplatin effectively prolonged survival of rats with F98 gliomas. Maximal treatment effect was seen with 5% loading of either polymer, with median survival increased threefold over control (P < 0.004). Systemic carboplatin also significantly prolonged survival, but the best intracranial polymer dose was significantly more effective than the best systemic dose tested. CONCLUSIONS: Carboplatin can be safely delivered intracranially by biodegradable sustained- release polymers. This treatment improves survival in rodents with experimental gliomas, with locally delivered carboplatin being more effective than systemic carboplatin.

HIV-associated primary CNS lymorbidity and utility of brain biopsy.

INTRODUCTION: Human immunodeficiency virus (HIV) infection is associated with several central nervous system (CNS) infections and neoplasms. These opportunistic processes generally occur with advanced immunosuppression, but if an accurate diagnosis is made, effective treatment can frequently be initiated. METHODS: In an attempt to assess the safety, diagnostic yield, and utility of stereotactic brain biopsy in the clinical management of suspected HIV-associated primary CNS lymphoma, we retrospectively studied the performance of biopsy in HIV-seropositive patients presenting with focal intracranial lesions. This analysis included 435 patients undergoing brain biopsy, identified through a local case series (n=47) combined with all published cases (n=388). The years of analysis for this study were 1984 and 1997. We also assessed the survival of HIV-associated intracranial mass lesions and of PCNSL patients treated at JHU. RESULTS: Definitive histopathological diagnoses were established in eighty-eight percent of biopsied cases: primary CNS lymphoma (PCNSL) (30%), CNS toxoplasmosis (CNS TOXO) (16%), progressive multifocal leukoencephalopathy (PML) (25%), and other specific diagnoses (17%). Post-biopsy morbidity within thirty days was 8.4% and mortality was 2.9%. PCNSL was the most common diagnosis among cases biopsied after failure of anti-toxoplasmosis therapy, 134/205 (65%). In the local case series, biopsy-related morbidity was associated with poor functional status, decreased platelet count, and number of lesions at presentation. The median survival of irradiated PCNSL cases was 29 days longer than untreated cases (median survival 50 days versus 21 days, respectively, Chi-square=6.73, P<0.01). DISCUSSION: Stereotactic brain biopsy had a high diagnostic yield for HIV-associated focal intracranial lesions, however, the biopsy complication rate in this patient population was relatively high. PCNSL was diagnosed in the majority of patients failing anti-toxoplasmosis therapy. Survival after irradiation for PCNSL remains very poor.

Intraventricular rupture of a purulent brain abscess: case report.

The mortality of patients with brain abscesses has decreased significantly from 38% in the 1950s to 25% in the 1980s (P = 0.003, Fisher's exact test by decade of report; asymptotic P values based on chi 2 distribution with 3 degrees of freedom, 28 series, 2825 total patients). This decrease in mortality has been attributed to improved diagnostic imaging, the evolution of neurosurgical techniques and understanding of intracranial pressure pathophysiology, greater critical care understanding, and newer antibiotics. However, the mortality associated with the intraventricular rupture of brain abscesses (IVROBA) remained consistently high (at or above 80% once IVROBA was identified) throughout these decades. Although 129 cases (84.5% mortality, 20 survivors) of IVROBA were located in these series and an additional six case reports of survival after IVROBA were found in the literature, treatment advice and detailed clinical description of these surviving cases are sparse or absent. A case of IVROBA with good quality of survival is presented along with the aggressive five-component therapeutic plan used. The five components are: 1) open craniotomy with debridement of abscess cavity, 2) lavage of the ventricular system, 3) 6 weeks of intravenous antibiotics, 4) intraventricular gentamicin twice daily for 6 weeks, and 5) intraventricular drainage for 6 weeks.

Intratumoral chemotherapy.

In an effort to improve survival from malignant gliomas, investigators have used intratumoral chemotherapy protocols to deliver high doses of tumoricidal agents directly to the brain. Theoretically, these infusions bypass the blood-brain barrier, minimize systemic drug levels and the side effects of chemotherapy, and achieve prolonged elevations of intracerebral chemotherapeutic agents relative to those obtainable by systemic administration. Almost all major classes of chemotherapeutic agents have been examined as possible intratumoral therapies via delivery approaches ranging from simple intratumoral injections to implantable computer-driven constant infusion pumps and biodegradable polymer matrices. In this review, we summarize the major clinical trials and experimental investigations underlying the development of intratumoral chemotherapy as a treatment for gliomas.

Impaired immunocompetence in patients with malignant gliomas: the possible role of Tg-lymphocyte subpopulations.

T-lymphocyte subpopulations (Tg or "suppressor cells" and Tm or "helper cells") in the peripheral blood of 16 patients with malignant intracranial gliomas were analyzed. The number of Tm-lymphocytes was very close to normal in both pre- and postoperative samples, whereas Tg-lymphocytes were significantly increased preoperatively (18.55 +/- 1.11 vs. 12.72 +/- 1.19 p less than 0.001) and were still slightly higher than normal after operation and radiation treatment. These preliminary findings suggest a possible role of T-suppressor lymphocytes in the impairment of cell-mediated immunocompetence that has been observed repeatedly in patients with malignant gliomas.

Cyclic nucleotides in medulloblastomas: correlative study of tumoral and cerebrospinal fluid levels.

The tumoral and cerebrospinal fluid (CSF) levels of cyclic nucleotides and of the main adrenergic metabolites (homovanillic acid and 5-hydroxyindoleacaetic acid) were investigated in a group of children with posterior fossa medulloblastomas. A longitudinal evaluation of CSF change of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and adrenergic metabolites before and after surgical removal of the tumor mass is presented. Some preliminary patterns concerning correlative levels in the neoplastic tissue are discussed. The relevant increase of cGMP in medulloblastoma specimens and in CSF samples operation and the rapid decrease in the CSF after surgical removal of the tumor seem to suggest a possible role of cyclic nucleotides in the neoplastic growth of these tumors. (Neurosurgery, 7: 359-362, 1980).

Well-differentiated papillary adenocarcinoma arising in a supratentorial enterogenous cyst: case report.

OBJECTIVE AND IMPORTANCE: We report a case of a well-differentiated papillary adenocarcinoma arising in an supratentorial enterogenous cyst. The clinicopathological features of this case and a brief review of the literature are presented. CLINICAL PRESENTATION: A 45-year-old woman presented with abrupt onset of sensory seizures and abnormal sensation on the left side of her face, left leg, and left arm. Radiological studies showed a cystic extraaxial tumor with mass effect in the right parietal area. The initial clinical impression was a metastatic lesion, and a comprehensive metastatic workup revealed no evidence of tumor elsewhere. INTERVENTION: A gross total resection of the solid cystic tumor was achieved by a frontoparietal craniotomy. Sixteen months after the initial surgery, the patient presented with signs of increased intracranial pressure and a large parietal cyst. The cyst was fenestrated at the time of the second craniotomy. CONCLUSION: A pathological study of the initial surgical material revealed it to be a well-differentiated papillary adenocarcinoma in association with an enterogenous cyst. The second surgical specimen consisted only of the benign cyst wall. The patient recovered uneventfully from the second surgery and was free of symptoms 6 months postoperatively. The importance of recognizing the rare possibility of malignant progression of a benign enterogenous cyst in the central nervous system is discussed.

Reversible posterior leukoencephalopathy occurring during resection of a posterior fossa tumor: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Our goal was to present a clinically and radiographically documented case of reversible posterior leukoencephalopathy (RPL) that occurred during resection of a posterior fossa tumor. Although RPL has been previously described in multiple nonsurgical settings, we hope that this case description makes RPL more clinically and radiographically recognizable to neurosurgeons. CLINICAL PRESENTATION: RPL is the clinical syndrome of headaches, altered mental status, seizures, and visual loss, with radiographic findings of reversible parieto-occipital changes on cerebral computed tomographic and magnetic resonance imaging scans. It has been previously reported in the settings of malignant hypertension, renal disease, eclampsia, and immunosuppression. To our knowledge, the patient presented represents the first clinically and radiographically documented case of RPL occurring during resection of a posterior fossa tumor. The patient intraoperatively exhibited wide fluctuations in blood pressure and awoke with clinical and radiographic findings consistent with RPL. INTERVENTION: Aggressive intraoperative and postoperative management of the patient's blood pressure, supportive intensive care, rehabilitation, and close radiographic follow-up were performed. CONCLUSION: RPL can occur as a result of intraoperative variations in blood pressure, even among young, previously healthy individuals. With the aforementioned interventions, the patient experienced significant clinical and radiographic recovery.

Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome presenting as a primary calvarial lesion. Case report and review of the literature.

The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.