James Dimou

Regulation of glycogen synthase kinase-3 beta (GSK-3β) by the Akt pathway in gliomas

Gliomas are aggressive brain tumours that, despite advances in multimodal therapies, continue to portend a dismal prognosis. Glioblastoma multiforme (GBM) represents the most aggressive glioma and patients have a median survival of 14 months, even with the best available treatments. The phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3 beta (GSK-3β) and Wnt/β-catenin pathways are dysregulated in a number of cancers, and these two pathways share a common node protein, GSK-3β. This protein is responsible for the regulation/degradation of β-catenin, which reduces β-catenins translocation to the nucleus and influences the subsequent transcription of oncogenes. The non-specific small-molecule GSK-3β inhibitor, lithium chloride (LiCl), and the specific Akt inhibitor, AktX, were used to treat U87MG and U87MG.Δ2-7 human glioma cell lines. LiCl treatment significantly affected cell morphology of U87MG and U87MG.Δ2-7 cells, while also increasing levels of phospho-GSK-3β in a dose-dependent manner. Increased cell proliferation was observed at low-to-mid LiCl concentrations as determined by MTT cell growth assays. Treatment of U87MG and U87MG.Δ2-7 cells with AktX resulted in reduced levels of phospho-GSK-3β through its inhibition of Akt, in addition to decreased levels of phosphorylated (active) Akt in a dose-dependent fashion. We have shown in this study that GSK-3β regulation by phosphorylation is important for cell morphology and growth, and that LiCl enhances growth of U87MG and U87MG.Δ2-7 cells by inhibiting GSK-3β through its phosphorylation, whereas AktX reduces growth via activation of GSK-3β by inhibiting Akts kinase activity.

Metastatic prostate adenocarcinoma invading an atypical meningioma.

Although prostate adenocarcinoma is the most commonly diagnosed cancer in men, intracranial metastases are rare. We describe a 72-year-old patient with known metastatic prostate cancer, presenting with a dural-based parafalcine lesion on radiological imaging, following a seizure. Total macroscopic excision of the lesion was achieved at surgery, with histopathology confirming prostate adenocarcinoma embedded in an atypical (World Health Organization Grade II) meningioma, fulfilling all the criteria for true tumour-to-tumour metastasis. To our knowledge, this is the first report of prostate cancer metastasising to an atypical meningioma.

Communication in and clinician satisfaction with multidisciplinary team meetings in neuro-oncology

Multidisciplinary Team (MDT) meetings are critical in the management of complex cancer cases. There are limited data regarding the effectiveness of neuro-oncology MDT meetings and the impact of documenting and disseminating the recommended patient management. We established a weekly neuro-oncology MDT meeting and developed a standard electronic communication process. A survey was issued to participating clinicians to assess their level of satisfaction. The survey revealed that 100% felt the meeting and its documentation was very or extremely important, and 94% (n=15) felt the meeting was effective in documentation and communication of plans. There was a mixed response regarding which patients should be discussed: 44% (n=7) thought all patients should be discussed and 56% (n=9) thought only those patients with complex management issues should be discussed. We have developed an efficient method of documenting and disseminating patient information arising from our neuro-oncology MDT meeting. Clinician satisfaction was high.

Spontaneous spinal epidural haematoma in a geriatric patient on aspirin

Spontaneous spinal epidural haematoma (SSEH) is a rare cause of spinal cord compression in adults, especially in the elderly. We report an independent 88-year-old female, on aspirin only for chronic atrial fibrillation, who presented with a 12-hour history of acute lumbar back pain, urinary incontinence and progressive bilateral lower limb paresis. Examination revealed saddle anaesthesia and reduced anal tone. Urgent spinal MRI demonstrated an epidural haematoma extending from T7 to L5. The patient made a poor initial post-operative recovery, but four months later had begun to mobilise independently after intensive physiotherapy. The case highlights the significance of clinical suspicion, especially in those patients on anti-platelet therapy, rapid spinal radiography and emergent decompressive surgery in SSEH patients, as well as the importance of ongoing rehabilitation in restoring neurological function.

A patient with delayed traumatic cervical spinal epidural haematoma presenting with hemiparesis

Delayed presentation of spinal epidural haematoma post-trauma is rare, and portends a significant management challenge for clinicians. A 57-year-old female presented 1 week after motor vehicle accident with a 24-hour history of progressive interscapular pain and right-sided hemiparesis. Urgent spinal MRI demonstrated an extensive epidural haematoma extending from C3 to T2. The patient made an excellent post-operative neurological recovery. The importance of clinical suspicion is highlighted, especially in patients presenting with unilateral neurological deficits, as well as expeditious spinal radiography (including CT scans) and emergent surgical treatment in achieving positive clinical outcomes.

Primary diffuse leptomeningeal gliosarcomatosis with a sphenoid/sellar mass: Confirmation of the ectopic glial tissue theory?

Gliosarcoma is a rare glioblastoma variant, classically arising in the cerebral hemispheres. We report a patient with primary diffuse leptomeningeal gliomatosis (PDLG) with a sphenoid sinus and sellar mass. An 84-year-old woman presented with progressive headache and right-sided visual failure, associated with ipsilateral oculomotor nerve palsy and left temporal field loss. Neuraxial MRI showed a large lesion within the sphenoid sinus and sella resulting in chiasmal compression, and diffuse cranial and spinal leptomeningeal enhancement. Endoscopic transphenoidal biopsy and debulking of the sphenosellar lesion was performed, and gliosarcoma was diagnosed on histopathological examination. The patient was palliated due to poor performance status. To our knowledge, this is the only report of gliosarcoma within the paranasal sinuses and the second report of PDLG where the histological analysis has confirmed gliosarcoma. We believe this adds significant weight to the theory that heterotopic nests of glial tissue, in this instance within the sphenoid or sella, are the putative origin of PDLG.

Recurrent malignant peripheral nerve sheath tumour in a patient with neurofibromatosis Type 1: A case report

Malignant peripheral nerve sheath tumour (MPNST) is a rare, albeit well-described, complication of neurofibromatosis. We report a 58-year-old patient with known neurofibromatosis Type 1 (NF-1) who presented with an aggressive recurrent malignant peripheral nerve sheath tumour and spinal cord compression 5 weeks after undergoing tumour excision with thoracic (T)6-7 laminectomy. The case and literature review are instructive to those following NF-1 patients with regards to screening for, and management of, malignant conversion of plexiform neurofibroma.

Sacral ganglioneuroma in a 19-year-old woman

Ganglioneuroma is a rare benign neural crest tumour, located usually in the posterior mediastinum and retroperitoneum. It tends to acquire significant size before symptoms or clinical signs become apparent. We report a 19-year-old female who underwent excision of a pelvisacral ganglioneuroma via a Pfannenstiel incision, after an abdominopelvic CT scan for investigation of left iliac fossa pain and menorrhagia detected a pelvic mass. This report highlights the importance of complete surgical excision of these lesions and the collaboration of multiple surgical units in managing these often large, variably located tumours.

Spinal cord compression as the initial presentation of acute biphenotypic leukaemia.

Acute biphenotypic leukaemia (BAL) is an uncommon haematological malignancy with features of myeloid and lymphoid origin and poor overall prognosis. We report a 68-year-old man who presented with rapidly progressive upper thoracic spinal cord compression secondary to an extradural lesion. A T2-3 decompressive laminectomy with tumour excision was performed. Histopathology confirmed the diagnosis of acute biphenotypic (B/myeloid) leukaemia. The patient had only minor post-operative improvement in pyramidal lower limb weakness. He succumbed to the disease three months post-diagnosis after failing induction chemotherapy. While central nervous system involvement with acute leukaemia is well recognised, this is the first reported patient with spinal cord compression secondary to this leukaemia subtype.

Metastatic olfactory neuroblastoma invading a radiation-induced meningioma

Olfactory neuroblastomas are malignant, neuroectodermal nasal tumours. We describe a 62-year-old patient with a recurrent olfactory neuroblastoma invading a radiation-induced meningioma. Given the temporal and spatial relationship between the primary lesion and the described recurrence, this was due to metastatic rather than direct contiguous spread, fulfilling all the criteria for true tumour-to-tumour metastasis. To our knowledge, this is the first description of an olfactory neuroblastoma metastasising to a meningioma.