Kate Drummond

Glutamate is associated with a higher risk of seizures in patients with gliomas

Objective: To investigate the relationship of glutamate and glutamate transporter expression in human gliomas and surrounding peritumoral brain to the presence of tumor-associated seizures (TAS). Methods: We studied a retrospective (group 1: 190 patients) and then a prospective (group 2: 98 patients) cohort of patients who underwent a craniotomy for a supratentorial glioma. Tumor and peritumor tissue specimens were assayed for glutamate concentration and expression of glial glutamate transporters. Differences between the seizure (TAS) and seizure-free (non-TAS) groups were compared. Results: A total of 42% of patients had TAS, with 95% of seizures first occurring preoperatively. Clinical factors independently associated with risk of TAS were younger age, temporal lobe location, and tumors with oligodendroglial components. Molecular features in tumor specimens associated with TAS were higher glutamate concentrations, reduced EAAT2 expression, and increased system Xc− expression. In group 2, these results were also replicated in the peritumor tissue. Logistic regression analysis identified raised glutamate concentrations in tumor and peritumor tissue, increased expression of peritumor system Xc−, younger age, temporal lobe location, and tumors with oligodendroglial components as independently predictive of preoperative seizures. Conclusion: Relative increased glutamate concentration in gliomas, and altered glutamate transporter expression, are associated with the presence of TAS and may play a mechanistic role in their pathogenesis.

Comparison between poor and long‐term survivors with glioblastoma: Review of an Australian dataset

Despite the largely poor prognosis for patients with glioblastoma, 5‐year survival approaches 10%. In many circumstances the reasons for discrepant outcomes remain unknown. This retrospective cohort study compared clinical and socio‐demographic variables between long‐term and poor survivors with glioblastoma.

MRI Grading versus Histology: Predicting Survival of World Health Organization Grade II–IV Astrocytomas

BACKGROUND AND PURPOSE: Histologic grading of intracranial astrocytomas is affected by sampling error and substantial inter- and intraobserver variability. We proposed that incorporating MR imaging into grading will predict patient survival more accurately than histopathology alone. MATERIALS AND METHODS: Patients with a new diagnosis of World Health Organization grades II–IV astrocytoma or mixed oligoastrocytoma diagnosed between September 2007 and December 2010 were identified. Two hundred forty-five patients met the inclusion criteria. Preoperative MRIs were independently reviewed by 2 readers blinded to the histologic grade, and an MR imaging grade was given. The MR imaging and histopathologic grades were compared with patient survival. RESULTS: Patients with grade II or III astrocytomas on histology but evidence of necrosis on MR imaging (consistent with a grade IV tumor) had significantly worse survival than patients with the same histology but no evidence of necrosis on MR imaging (P = .002 for grade II histology and P = .029 for grade III). Their survival was not significantly different from that in patients with grade IV tumors on histology (P = .164 and P = .385, respectively); this outcome suggests that all or most are likely to have truly been grade IV tumors. MR imaging evidence of necrosis was less frequent in grade II and III oligoastrocytomas, preventing adequate subgroup analysis. CONCLUSIONS: MR imaging can improve grading of intracranial astrocytomas by identifying patients suspected of being undergraded by histology, with high interobserver agreement. This finding has the potential to optimize patient management, for example, by encouraging more aggressive treatment earlier in the patients course.

Neurosurgical considerations in von Hippel–Lindau disease

Von Hippel-Lindau disease is an inherited syndrome predisposing to a variety of benign and malignant neoplasms of the central nervous system and viscera that requires comprehensive screening and follow-up of individuals and their families. As such, it is important for the neurosurgeon to be aware of its clinical features and management issues. In this article we review the clinical aspects, management and surveillance of von Hippel-Lindau disease for neurosurgical practice.

P2X7 receptors are a potential novel target for anti-glioma therapies

BackgroundHuman gliomas pose significant morbidity and mortality to those afflicted by them, and currently there are no curative treatment modalities available for these highly invasive tumours.MethodsWith the approval from the human ethics committee, patients diagnosed with brain tumour (glioma) were recruited for this study. At the time of surgical resection, freshly resected tumour as well as ‘peri-tumour’ tissue were taken directly from theatre to the laboratory and were successfully cultured. Confocal fluorescence microscopy techniques and immunohistochemistry were used for characterization of human glioma cultures. Dye uptake experiments and confocal microscopy were utilized for P2X7 receptor (P2X7R) pore activity.ResultsWe reveal human glioma cultures to contain microglia in close association with glioma (tumour) cells. Both glioma cells and microglia were found to express the purinergic, ATP sensing, P2X7R. P2X7R protein expression was increased in microglia derived from tumour when compared to ‘peri-tumour’ tissue. The pore capacity of P2X7R in tumour-associated microglia was functional, as evidenced by dye uptake experiments. Importantly, inhibition of P2X7R with the synthetic antagonist, brilliant blue G (BBG) resulted in a significant decrease in the number of glioma cells in culture.ConclusionsP2X7R was found to be over-expressed in grade IV human gliomas and its pore capacity was functional. Antagonism of P2X7R with BBG resulted in a decrease in tumour cell number. This identifies P2X7R as a promising therapeutic target to combat human glioma proliferation.

Glutamate quantification in patients with supratentorial gliomas using chemical shift imaging

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies.

Art macabre: Is anatomy necessary?

The late Sir Sydney Sunderland, Professor of Anatomy at Melbourne University, would be writhing in his grave and threatening resurrection by some mystical force if he knew that ‘postmodernism’ had invaded the teaching of anatomy in his former precincts. Sunderland was a charismatic genius who delivered spellbinding lectures of great eloquence using only his voice, coloured chalks and a blackboard. He was also a fervent advocate of a two year stint of cadaver dissection for all medical students and regarded this as essential for surgeons. Sunderland looked many a student in the eye and said, ‘ The surgeon must know his way around ’. Over the ages acquisition of cadavers has always been a contentious practice. Yet even the most macabre efforts to obtain bodies pale into insignificance in comparison to the everyday atrocities of the modern world. In addition, the good enabled by the use of cadavers far outweighs the distasteful aspects. It was crucial to the work of the Hunter brothers and thus contributed to the establishment of modern British surgery. At a recent hand surgery meeting the audience was treated to a high-tech demonstration of the anatomy of the wrist joint. The computer-based presentation utilized simulation, models, graphic design and a professional narrator. It was superb and won a prize. As a vision of carpal anatomy and dynamics is was true and a win for postmodernism. But for a practising surgeon dissecting a palmar ganglion stalk tentacling its way towards dorsolateral ligaments it was not a true picture of the real anatomy of the wrist ligaments. These ligaments are notoriously difficult to delineate. This writer would not demean the rightful place of simulation in teaching, especially in situations in which simulation approximates ‘real’ situations. Flight simulators can accurately mimic the physical sensations caused, for example by unexpected descent due to engine failure. The situation is similar for cardiopulmonary resuscitation. Deep-seated neurosurgical dissection, cardiac surgery and many other cases are amenable to simulation because of the mediating significance of display and endoscopic instrumentation. Other examples, such as microsurgery, seem to require both traditional anatomical knowledge and laboratory simulation of neurovascular anastomosis. However, many surgical techniques are more vagarious due to the almost infinite variations in human anatomy. Dissection of a pancreatic or other deep tumour is a more difficult proposition and could not be adequately simulated. Would a surgeon of the calibre of Norman C. Tanner, feeling by tactile gnosis around the lesser sac, or, for that matter, D.G. Bradman, have learned the precisions of their skills without decades of practise with the ‘real thing’.

Ovarian hyperstimulation syndrome leading to ventriculoperitoneal shunt malfunction: Case report

Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure for hydrocephalus. Unfortunately, VPS malfunction is not uncommon, with an estimated cumulative rate of 32% at 5 years. As flow through the shunt is influenced by the pressure gradient between the ventricles and the peritoneal cavity, malfunction may be caused by elevated intra-abdominal pressure. We present a rare patient with ascites following ovarian hyperstimulation syndrome (OHSS) leading to shunt malfunction. OHSS is a potentially life-threatening complication of controlled ovarian stimulation caused by the administration of exogenous gonadotropins. In this patient clinical and radiological resolution of shunt dysfunction were achieved following peritoneocentesis. To our knowledge this is the first described case of OHSS leading to shunt malfunction, emphasizing the importance of awareness, early recognition and proper management of abdominal etiologies of VPS malfunction.

Solid non-enhancing cerebellar pilocytic astrocytoma case report

Pilocytic astrocytomas (PA) are slow-growing low-grade gliomas, commonly diagnosed as cerebellar tumors among the pediatric and adolescent population. Characteristic neuroradiologic findings in PA include a cystic mass with enhancing solid nodule. While uncommon radiologic features of PA, including non-enhancing cystic tumors, have been previously described, we present a unique case of a patient with a non-enhancing solid cerebellar PA. The main clinical, radiologic, and pathologic findings are discussed and the relevant literature reviewed. To our knowledge, this is the first reported patient with these radiologic features of PA, highlighting the need for awareness of uncommon presentations when discussing differential diagnosis and pre-operative planning for cerebellar tumors in the relevant age group.

Intraparenchymal infratentorial ependymoma

Ependymomas are glial series tumours that can occur throughout the neural axis, usually in close proximity to the ventricles or central canal. While the fourth ventricle is a common location for ependymoma, we present a rare case of an entirely intraparenchymal infratentorial tumour, remote from the ventricular surface, and discuss the imaging characteristics that may suggest the diagnosis. The histological features, which remain identical despite the varied morphology of intraventricular versus intraparenchymal tumours, are also considered.