Martin R. MacFarlane

The neuro‐cardio‐endocrine response to acute subarachnoid haemorrhage

objective Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH.

Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma

The molecular basis for alternative lengthening of telomeres (ALT), a prognostic marker for glioma patients, remains unknown. We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom. Tumor samples were analyzed with respect to telomerase activity, telomere length, and ALT-associated promyelocytic leukemia nuclear bodies to determine their TMM. TP53 mutation was analyzed by direct sequencing of coding exons 2 to 11. We found an association between TP53 mutation and ALT mechanism and between wild-type TP53 and telomerase and absence of a known TMM (P < 0.0001). We suggest that TP53 deficiency plays a permissive role in the activation of ALT.

The CDKN2A G500 Allele Is More Frequent in GBM Patients with No Defined Telomere Maintenance Mechanism Tumors and Is Associated with Poorer Survival

Prognostic markers for glioblastoma multiforme (GBM) are important for patient management. Recent advances have identified prognostic markers for GBMs that use telomerase or the alternative lengthening of telomeres (ALT) mechanism for telomere maintenance. Approximately 40% of GBMs have no defined telomere maintenance mechanism (NDTMM), with a mixed survival for affected individuals. This study examined genetic variants in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene that encodes the p16INK4a and p14ARF tumor suppressors, and the isocitrate dehydrogenase 1 (IDH1) gene as potential markers of survival for 40 individuals with NDTMM GBMs (telomerase negative and ALT negative by standard assays), 50 individuals with telomerase, and 17 individuals with ALT positive tumors. The analysis of CDKN2A showed NDTMM GBMs had an increased minor allele frequency for the C500G (rs11515) polymorphism compared to those with telomerase and ALT positive GBMs (p = 0.002). Patients with the G500 allele had reduced survival that was independent of age, extent of surgery, and treatment. In the NDTMM group G500 allele carriers had increased loss of CDKN2A gene dosage compared to C500 homozygotes. An analysis of IDH1 mutations showed the R132H mutation was associated with ALT positive tumors, and was largely absent in NDTMM and telomerase positive tumors. In the ALT positive tumors cohort, IDH1 mutations were associated with a younger age for the affected individual. In conclusion, the G500 CDKN2A allele was associated with NDTMM GBMs from older individuals with poorer survival. Mutations in IDH1 were not associated with NDTMM GBMs, and instead were a marker for ALT positive tumors in younger individuals.

Intra-cerebroventricular captopril reduces plasma acth and vasopressin responses to hemorrhagic stress

The role of the brain renin-angiotensin system in mediating the peripheral hormone response to acute hemorrhagic stress (15 ml/kg over 10 min) was studied in 6 sheep during an intracerebroventricular infusion (2.8 micrograms/min) of the angiotensin-converting enzyme inhibitor, captopril. When compared with control experiments the plasma ACTH and vasopressin (AVP) response to hemorrhage was markedly reduced and delayed during icv captopril, which did not affect the response of plasma angiotensin II (AII). These results suggest that the normal and rapid response in ACTH and AVP secretion accompanying hemorrhagic stress is dependent on increased brain production of AII.

Facial nerve function and hearing preservation after retrosigmoid excision of vestibular schwannoma: Christchurch Hospital experience with 97 patients.

Background:  Between January 1988 and December 2002, 97 patients underwent surgery for excision of vestibular schwannoma via the retrosigmoid approach at Christchurch Hospital.

Chronic subdural haematomas are more common on the left than on the right

Subdural haematomas (SDHs), and in particular chronic subdural haematomas (CSDHs), are commonly encountered in a neurosurgical practice. The aetiology, presentation, management and prognosis of these are well documented but there are few publications that report on their side prevalence (laterality). We report an analysis of all patients (both operated on and conservatively managed) who presented to the Neurosurgical Service at Christchurch Hospital with SDHs between 1 January 1996 and 30 June 2006. A total of 413 patients presented with a total of 450 SDHs, of which 150 (33.3%) were acute, 38 were (8.4%) subacute and 262 (58.2%) were chronic. The patients ranged in age from 3 months to 95 years. The mean (+/-standard deviation, SD) age of patients with acute SDH was 50.9+/-25.8 years, 65.4+/-19.8 years for subacute SDH and 68.9+/-19.7 years for chronic SDH. A total of 275 (67%) patients were male and 138 (33%) female, with the male predominance occurring in all subgroups. The SDHs were distributed unilaterally in the acute and subacute groups; however, CSDHs occurred more frequently on the left side (57.2% compared to 42.7% on the right; p=0.0345). We discuss the likely reasons behind the increased rate of CSDHs diagnoses on the left side.

Excision of high and mid cervical spinal cord arteriovenous malformations by anterior operation

Symptomatic cervical spinal arteriovenous malformations (AVMs) located on the anterior aspect of the spinal cord are rare and surgical removal of these AVMs presents considerable challenges and risks. Surgical techniques to date have usually been by posterior approach and lateral dissection around the cord or via midline myelotomy, both approaches involving cord manipulation and retraction and in the latter, dissection through the spinal cord. We present two teenage patients with symptomatic anteriorly placed mid to high cervical spinal AVMs and associated aneurysm in which excision of the AVMs and aneurysm was performed by an anterior approach using vertebrectomy/corpectomy. The first case had a small perimedullary glomus-type AVM with an aneurysm on the anterior aspect of the cord at the C3/4 level; excision was performed using a single level vertebrectomy/corpectomy, the patient remaining neurologically intact. The second case had a medium-sized juvenile AVM with an aneurysm, both perimedullary and intramedullary, centred at the C5/6 level; excision was performed using a two-level vertebrectomy/corpectomy with no deterioration in the marked pre-operative tetraparesis, which at long-term follow up had improved and stabilised. Anterior approaches have been recently described for treatment of anteriorly placed cervical arteriovenous fistulas (AVFs) and an intramedullary haemangioblastoma, but not as yet for spinal AVMs. These are the first two reported cases of anteriorly situated cervical AVMs successfully removed surgically by an anterior approach and with good neurological outcomes.

Intraosseous lipoma of the body of the sphenoid bone

A case of intraosseous lipoma arising from the body of the sphenoid bone with intrasellar and suprasellar components is reported. This is the first report of this uncommon tumour occurring in an atypical intracranial site, producing the locally invasive and pressure effects of visual failure and hypopituitarism. The diagnosis was based on computed tomographic (CT) and magnetic resonance (MR) imaging with histological confirmation following frontal craniotomy.

Intraventricular meningioma with drop metastases and subgaleal metastatic nodule.

We report a case of malignant intraventricular meningioma with CSF drop metastases and an implantation metastatic subgaleal nodule in a 53-year-old woman. Malignant intraventricular meningiomas are rare with only seven cases being reported in the literature. These tumours can be very aggressive and one should consider immediate postoperative radiotherapy.

Pontomedullary ganglioglioma : A rare tumour in an unusual location

Gangliogliomas are rare low-grade tumours composed of neoplastic glial and neuronal cell elements. Although they may arise within any part of the neuraxis, involvement of the brainstem is rarely encountered. The distinct nature of gangliogliomas means that they have a comparatively better prognosis than other tumours in this location following subtotal resection. We present the case of an infant with a pontomedullary ganglioglioma and discuss the relevant literature.