Complication of Middle Cerebral Artery Aneurysm Surgery: An M2 Tear at the Neck, Managed with a Salvage M2-to-M2 In Situ Bypass.

An unexpected rupture at the aneurysm neck, with or without adjacent arterial injury or compromise of distal branches during microsurgical clipping, can be a challenging surgical problem to resolve. In this presented case of a neurologically intact 65-year-old woman, elective clipping of an unruptured right middle cerebral artery bifurcation aneurysm was complicated by an unexpected M2 tear at the neck, involving the origin of the frontal M2. Attempts to seal the tear directly, using various techniques, failed; therefore, it was ultimately managed with sacrifice of the vessel and a salvage side-to-side M2-to-M2 in situ bypass. Six months after surgery, the patient demonstrated moderate disability but was able to ambulate with a cane.

Endoscopic-assisted evacuation of subdural collections.

Treatment of chronic subdural haematoma (SDH) using endoscopic-assisted techniques is a minimally invasive method that may provide an addition to the standard technique of burr-hole craniostomy drainage. Over a 12-month period the authors used endoscopic assistance with burr-hole craniostomy drainage, and prospectively collected data to review the technique. Ten patients were treated during the study, with an average age of 67. Subsequent to the study, one further procedure was performed on a 79-year-old man. Although endoscopic assistance did not alter the intra-operative plan in most patients, it did assist with inserting a subdural catheter for washout of the subdural space, assessing for multi-loculation of the SDH and providing visual images that were captured for discussion with the patient/family and for later study. In one patient, endoscopy assisted with the visualisation and destruction of neomembranes. We conclude that the technique is unlikely to alter the surgeon's pre-operative or intra-operative plan; however, in selected circumstances, it could make the procedure safer with enhanced intra-operative visualization and may also allow for the identification and destruction of neomembranes or solid clots under direct vision.

Cervical arthroplasty for myelopathy adjacent to previous multisegmental fusion.

In recent years, there has been increasing interest in the use of cervical arthroplasty for the treatment of degenerative cervical pathology. In its relative infancy, the applications for this technique are still being explored. In this report, we present the use of cervical arthroplasty in the treatment of progressive cervical myelopathy due to adjacent segment disease related to previous multisegmental fusion.

Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment.

While treatment with surgery, radiotherapy and/or chemotherapy may prolong life for patients with glioblastoma, recurrence is inevitable. What is still being discovered is how much these treatments and recurrence of disease affect the molecular profiles of these tumors and how these tumors adapt to withstand these treatment pressures. Understanding such changes will uncover pathways used by the tumor to evade destruction and will elucidate new targets for treatment development. Nineteen matched pre-treatment and post-treatment glioblastoma tumors were subjected to gene expression profiling (Fluidigm, TaqMan assays), MGMT promoter methylation analysis (pyrosequencing) and protein expression analysis of the DNA repair pathways, known to be involved in temozolomide resistance (immunohistochemistry). Gene expression profiling to molecularly subtype tumors revealed that 26% of recurrent post-treatment specimens did not match their primary diagnostic specimen subtype. Post-treatment specimens had molecular changes which correlated with known resistance mechanisms including increased expression of APEX1 (p < 0.05) and altered MGMT methylation status. In addition, genes associated with immune suppression, invasion and aggression (GPNMB, CCL5, and KLRC1) and polarization toward an M2 phenotype (CD163 and MSR1) were up-regulated in post-treatment tumors, demonstrating an overall change in the tumor microenvironment favoring aggressive tumor growth and disease recurrence. This was confirmed by in vitro studies that determined that glioma cell migration was enhanced in the presence of M2 polarized macrophage conditioned media. Further, M2 macrophage-modulated migration was markedly enhanced in post-treatment (temozolomide resistant) glioma cells. These findings highlight the ability of glioblastomas to evade not only the toxic onslaught of therapy but also to evade the immune system suggesting that immune-altering therapies may be of value in treating this terrible disease.

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response. This may be due to intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion. Aberrations in other DNA repair mechanisms may also contribute. This study investigated intratumoral heterogeneity in multiple glioblastoma tumors with a particular focus on the DNA repair pathways. Transcriptional intratumoral heterogeneity was identified in 40% of cases with variability in MGMT methylation status found in 14% of cases. As well as identifying intratumoral heterogeneity at the transcriptional and epigenetic levels, targeted next generation sequencing identified between 1 and 37 unique sequence variants per specimen. In-silico tools were then able to identify deleterious variants in both the base excision repair and the mismatch repair pathways that may contribute to therapeutic response. As these pathways have roles in temozolomide response, these findings may confound patient management and highlight the importance of assessing multiple tumor biopsies.

Molecular heterogeneity in glioblastoma: potential clinical implications.

Glioblastomas, (grade 4 astrocytomas), are aggressive primary brain tumors characterized by histopathological heterogeneity. High-resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

We present the unusual case of a 33-year-old woman who presented with a 2 year history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later, the lesion had enlarged by 5mm, with associated enhancement of the dura of the planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

Cervical disc arthroplasty for the treatment of spondylotic myelopathy and radiculopathy.

The concept of cervical disc arthroplasty (CDA) for the anterior treatment of cervical pathology has existed for approximately half a decade. In this time, multiple devices have been developed for this purpose, with the ultimate aim to provide an alternative to fusion. Fifty-five patients with cervical spondylotic radiculopathy and myelopathy underwent CDA over a 5 year period. Data was collected on 46 patients, which included Visual Analogue Scale scores for neck pain and arm pain, Neck Disability Index scores, Short Form-36 v2 (SF-36) and Nurick grades for myelopathy patients. Preoperative data and data obtained at the latest clinical follow-up (median 48 months, range, 10-76 months) were analysed to assess the intermediate term efficacy of the procedure. In patients with radiculopathy, arm pain improved by 88% (p<0.001). In those presenting with myelopathy, the Nurick grades improved from a median of 1 to 0 (p<0.001). In both groups of patients, improvements in pain and neurologic deficit were accompanied by significant improvements in multiple domains of the SF-36. Using a composite system which considered neck pain, arm pain, function and myelopathy, we arrived at an overall success rate of 73%. We concluded that CDA is an effective intervention for improving neurologic deficit, arm pain and local neck symptoms that translated into improvements in physical and social functioning in the intermediate term.

Lumbar chordoma mimicking a neurogenic tumour.

Chordomas are rare tumours arising from the primitive notochord along the axial skeleton, typically from the sacrococcygeal region, spheno-occipital region and less commonly, the mobile spine. Midline location associated with bony involvement with extension to the surrounding tissues is the norm. Chordomas presenting laterally, centred within the neural exit foramen and extending to the paraspinal muscles without significant vertebral involvement is rare. We present a 60-year-old woman with lower back pain and radiculopathy. Imaging revealed a unilateral lesion at L4/5 extending through the left neural exit foramen into the paraspinal region. There was only minimal apparent bony involvement. Though these features were highly suggestive of a neurogenic tumour, histopathology revealed the lesion to be a chordoma. Excision of the tumour was performed under neurophysiological monitoring.

Phrenic nerve stimulation: the Australian experience.

Phrenic nerve stimulation is a technique whereby a nerve stimulator provides electrical stimulation of the phrenic nerve to cause diaphragmatic contraction. The most common indications for this procedure are central alveolar hypoventilation and high quadriplegia. This paper reviews the available data on the 19 patients treated with phrenic nerve stimulation in Australia to date. Of the 19 patients, 14 required pacing due to quadriplegia, one had congenital central hypoventilation syndrome and one had brainstem encephalitis. Information was unavailable for the remaining three patients. Currently, 11 of the pacers are known to be actively implanted, with the total pacing duration ranging from 1 to 21 years (mean 13 years). Eight of the 19 patients had revision surgeries. Four of these were to replace the original I-107 system (which had a 3-5-year life expectancy) with the current I-110 system, which is expected to perform electrically for the patient's lifetime. Three patients had revisions due to mechanical failure. The remaining patients' notes were incomplete. These data suggest that phrenic nerve stimulation can be used instead of mechanical ventilators for long-term ongoing respiratory support.

Spontaneous cerebellar haemorrhage following lumbar fusion.

Spontaneous cerebellar haemorrhage following spinal surgery is rare, with fewer than 20 patients reported in the literature. We present a 70-year-old woman who underwent a L5-S1 posterior lumbar interbody fusion for spondylolisthesis. Intraoperatively, an incidental durotomy occurred and was repaired uneventfully. A large amount of serosanguinous fluid was noted in the subfascial drain post-operatively. The patient became increasingly drowsy 36 hours later. She was subsequently found to have bilateral cerebellar haemorrhages with associated non-communicating hydrocephalus.

Isolated neurolymphomatosis of the cauda equina and filum terminale: case report.

STUDY DESIGN: Case report. OBJECTIVE: We report the case of a previously healthy 16-year-old boy who presented with back pain and decreased mobility. Magnetic resonance imaging (MRI) revealed an extensive intradural lesion in the region of the thoracolumbar junction. SUMMARY OF BACKGROUND DATA: Neurolymphomatosis is a rare but well-described entity in which malignant lymphocytes, more commonly of B-cell lineage, infiltrate the peripheral nervous system. Isolated involvement of spinal nerve roots and subsequent clinical presentation directly due to this is unusual, and there have been few such published cases. METHODS: Retrospective case study with follow-up examination at 6-months and 1-year. RESULTS: The patient was transferred directly to the operating theater from MRI for urgent decompressive laminectomy. Diagnosis of neurolymphomatosis of the cauda equina and filum terminale by diffuse large B-cell lymphoma was confirmed by histopathology. The patient received adjuvant chemotherapy and radiotherapy. At 6- and 12-month follow-up, the patient's back pain had resolved and lower limb function was improving slowly. MRI revealed no evidence of residual or recurrent disease. CONCLUSION: This case highlights the importance of prompt diagnosis through high-resolution imaging, as well as the role of emergent neural decompression once a diagnosis of spinal cord compression has been established (regardless of the ultimate cause). It exposes some of the diagnostic pitfalls associated with the imaging of unusual spinal lesions, and it underlines the importance of obtaining an urgent and accurate tissue diagnosis to allow for the instigation of appropriate medical therapy.