Sarcoidosis presenting with acute hydrocephalus in a New Zealand European female.

Hydrocephalus as the presenting feature of sarcoidosis is extremely rare. We report the case of a 41-year-old New Zealand European female who presented with acute hydrocephalus as the first manifestation of systemic sarcoidosis.

Increased paired box transcription factor 8 has a survival function in glioma.

BACKGROUND: The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis. METHODS: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression. RESULTS: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death. CONCLUSIONS: PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

Use of recreational drug 1,3 Dimethylamylamine (DMAA) [corrected] associated with cerebral hemorrhage.

Dimethylamylamine (DMAA) was a forgotten pharmaceutical that was patented in 1944 as a nasal decongestant. DMAA has recently gained popularity as a dietary supplement, with claims of effectiveness as an athletic performance enhancer and weight loss aid. It is also sold as a recreational stimulant drug. DMAA is a sympathomimetic and potent pressor agent. This report describes 3 cases of cerebral hemorrhage in adults after the use of DMAA. The status of this substance as a synthetic or naturally occurring compound is also discussed.

Ultra-early (within 24 hours) aneurysm treatment after subarachnoid hemorrhage.

BACKGROUND: The timing of definitive aneurysm treatment (coiling or clipping) in acute aneurysm subarachnoid hemorrhage was a subject of controversy. Although most vascular neurosurgeons agreed on early aneurysm treatment (within the first 72 hours), whether ultra-early aneurysm treatment (within the first 24 hours) was beneficial remained debatable. We aimed to investigate whether ultra-early aneurysm treatment is associated with better neurological outcome in all patients or only good-grade patients or only poor-grade patients. METHODS: Two-hundred and seventy-six (84%) patients had hemorrhage onset time and aneurysm treatment time available for analysis. Values of P < 0.05 were taken as statistically significant, and P values between 0.05 and 0.10 were considered to be a trend. RESULTS: For the 96 poor-grade (World Federation of Neurological Surgeons grading scale 4 to 5) patients, there was a significant association between Short Form-36 mental scores and ultra-early aneurysm treatment (50 ± 10 vs. 46 ± 10, P = 0.019) and a trend toward association between ultra-early surgery and favorable neurological outcome (odds ratio 2.4 [95% confidence interval 1.0 to 6.0], P = 0.062). A reduction in clinical rebleeding (12% vs. 22%, P = 0.168) was observed in patients undergoing ultra-early aneurysm treatment. CONCLUSIONS: Aneurysm treatment performed within the 24-hour window may be associated with a better outcome and halve the clinical rebleeding risk in poor-grade aneurysmal subarachnoid hemorrhage patients.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis.

INTRODUCTION: Previous meta-analyses of magnesium sulphate infusion in the treatment of aneurysmal subarachnoid hemorrhage (SAH) have become outdated due to recently published clinical trials. Our aim was thus to perform an up-to-date systemic review and meta-analysis of published data on the use of magnesium sulphate infusion in aneurysmal SAH patients. METHODS: A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of magnesium sulphate infusion in aneurysmal SAH patients. The results were analyzed with regard to delayed cerebral ischemia (DCI), delayed cerebral infarction, and favorable neurological outcomes at three and six months. The risks of bias were assessed using the Jadad criteria, with a Jadad score >3 indicating a lower such risk. Meta-analyses are presented in terms of relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Six eligible studies with 875 patients were reviewed. The pooled RR for DCI was 0.87 (95% CI, 0.36 to 2.09; P = 0.75). That for delayed cerebral infarction was 0.58 (95% CI, 0.35 to 0.97; P = 0.04), although this result did not persist if only randomized clinical trials with a lower risk of bias were included (RR 0.61, 95% CI, 0.31 to 1.22; P = 0.17). The pooled RR for a favorable outcome at three months was 1.14 (95% CI, 0.99 to 1.31; P = 0.07), and that for a favorable outcome at six months was 1.08 (95% CI, 0.94 to 1.24; P = 0.29). CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation.

Health-related quality of life after aneurysmal subarachnoid hemorrhage: profile and clinical factors.

BACKGROUND: Health-related quality of life has recently been suggested as a supplement to the traditional neurological outcome measures from the patient's perspective according to the World Health Organization model and may capture the effects of other factors such as posttraumatic stress disorder and neuroendocrine dysfunction. OBJECTIVE: To explore the profile and clinical factors of quality of life after aneurysmal subarachnoid hemorrhage using the data we obtained from the recently completed Intravenous Magnesium Sulphate After Aneurysmal Subarachnoid Hemorrhage (IMASH) trial. METHODS: This study was registered at www.strokecenter.org/trials and www.ClinicalTrials.gov (NCT00124150). Data from a patient cohort obtained with the Short Form-36 questionnaire completed at 6 months were used for analysis. RESULTS: Patients with aneurysmal subarachnoid hemorrhage demonstrated a decrease in quality of life according to the Short Form-36 at 6 months. The physical and mental health scores correlated with the Extended Glasgow Outcome Scale and had the potential to avoid the ceiling effect. Multiple regression analyses showed that the physical component scores were related to age, World Federation of Neurological Surgeons grade, and chronic hydrocephalus and that the mental component scores were not related to the traditional prognostic factors. CONCLUSION: Subarachnoid hemorrhage caused a decrease in quality of life. Chronic hydrocephalus is related to a decrease in physical health quality of life.

Plasma magnesium concentrations and clinical outcomes in aneurysmal subarachnoid hemorrhage patients: post hoc analysis of intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage trial.

BACKGROUND AND PURPOSE: Conflicting data have been obtained on optimal plasma magnesium concentrations for clinical outcomes in patients with aneurysmal subarachnoid hemorrhage. METHODS: Adults (aged 18 years or older) who had acute aneurysmal subarachnoid hemorrhage diagnosed were randomly assigned to receive either an intravenous MgSO(4) infusion (80 mmol in 500 mL normal saline per day) or a placebo (500 mL normal saline per day) for up to 14 days. Post hoc multivariable binary logistic regression analyses were performed by dividing mean plasma magnesium concentrations into 4 quartiles according to treatment group and then comparing with the lowest quartiles. RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial.

BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. METHODS: We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). RESULTS: Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.

The effect of intravenous magnesium sulfate infusion on serum levels of sodium and potassium in patients with aneurysmal subarachnoid hemorrhage.

Abnormal serum sodium levels are frequently observed among patients with aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema or mass effect. Low serum potassium levels (hypokalemia) are also common among patients with aneurysmal SAH and are associated with prolonged QT interval and ventricular arrhythmia. Recent meta-analysis suggests that MgSO4 infusion improves the clinical outcome in patients after aneurysmal SAH; however, MgSO4 infusion may theoretically exacerbate electrolyte disturbance. We retrospectively reviewed the prospectively collected demographic and laboratory data of 100 patients after aneurysmal subarachnoid SAH in a neurosurgical center in Hong Kong. 51 patients had daily magnesium sulfate infusion for 14 days (Group 1) and 49 patients were managed similarly, without magnesium sulfate infusion (Group 2). Days of hypernatremia (mean+/-SD) were 2.0+/-2.7 for group 1 and 2.0+/-2.5 for group 2, p = 0.999; days of hyponatremia (mean+/-SD) were 2.7+/-3.1 for group 1 and 2.0+/-2.9 for group 2, p = 0.230; days of hypokalemia (mean+/-SD) were 4.5+/-3.1 for group 1 and 4.5+/-3.2 for group 2, p = 0.819. Hyperkalemia was uncommon in both groups. There was also no statistically significant difference between the two groups when the data were re-analyzed as severe hyponatremia, severe hypokalemia and severe hyperkalemia. Magnesium sulfate infusion was safe and did not seem to exacerbate the duration of electrolyte disturbance associated with aneurysmal subarachnoid hemorrhage.

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.

Magnesium therapy within 48 hours of an aneurysmal subarachnoid hemorrhage: neuro-panacea.

Whereas advances in neurosurgical treatment and intensive care management improve the results from many of the devastating complications associated with aneurysmal subarachnoid hemorrhage, cerebral vasospasm remains a major cause of neurological morbidity and mortality. Experimental studies suggested that MgSO(4) inhibits excitatory amino acid release, blocks N-methyl-D-aspartate (NMDA) receptors and prevents calcium entry into the cell. Magnesium also increases red blood cell deformability. These changes may reduce the occurrence of cerebral vasospasm and minimize neuronal injury during episodes of cerebral vasospasm. Our group is currently hosting the intravenous magnesium sulfate to improve outcome after aneurysmal subarachnoid hemorrhage (IMASH) trial, which is a randomized, placebo-controlled, double-blinded, multicentered trial to evaluate the effect of magnesium sulfate infusion on the clinical outcome of patients with aneurysmal subarachnoid hemorrhage since 2002. The pilot result showed a trend towards decreased clinical vasospasm and better patient outcome. Magnesium sulfate infusion may prove to be an effective and inexpensive way to reduce the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage, which is a major breakthrough in the current management.

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study.

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH).Sixty patients with SAH were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded. Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.

Combined surgical and endovascular treatment of a posterior fossa dural arteriovenous fistula.

Posterior fossa dural arteriovenous fistulae (DAVF) are uncommon lesions. In the past, treatment of these lesions has involved both surgical and endovascular techniques, the latter being favoured in contemporary neurovascular medicine. We describe our experience in the case of a 71-year-old woman with a posterior fossa DAVF who presented with sudden onset headache, collapse and neurological deficit secondary to a subarachnoid haemorrhage. She was treated by means of direct surgical access of the lesion combined with endovascular occlusion resulting in a radiological and clinical cure.

Contrast enhancement of the spinal cord in a patient with cervical spondylotic myelopathy.

We wish to report a patient with cervical spondylotic myelopathy that demonstrated contranst enhancement on MRI which resolved following a decompressive procedure.

Lumbosacral clear-cell meningioma treated with subtotal resection and radiotherapy.

We wish to report a rare case of clear-cell meningioma in the lumbosacral region in a 34-year-old male patient who presented to us with lower back pain and leg pain. The management of the patient will be reported and histological appearance discussed. This rare tumour in a difficult anatomical position presents a challenge that requires management in a multidisciplinary fashion.

Postembolization hemorrhage of a large and necrotic meningioma.

Microparticulate embolization of meningiomas is a useful preoperative measure, but the potential risk of hemorrhagic complications should be recognized and balanced against the benefits. We report a case of subarachnoid hemorrhage occurring immediately after the embolization of a meningioma. Techniques for early diagnosis, such as CT, and early surgical intervention are crucial to a promising outcome. Large-size and necrotic or cystic components of a meningioma are probable risk factors that demand special consideration.

Intracranial aneurysms treated with Guglielmi detachable coils: midterm clinical and radiological outcome in 97 consecutive Chinese patients in Hong Kong.

BACKGROUND AND PURPOSE: Use of Guglielmi detachable coils (GDCs) has proved to be a promising endovascular treatment for intracranial aneurysms. This study aimed to evaluate midterm clinical and radiologic outcomes of this treatment in Hong Kong Chinese patients, 68% of whom had small aneurysms (< or =5 mm). METHODS: We included 97 consecutive patients in whom GDCs were placed with curative intent. The patients presented with subarachnoid hemorrhage (n = 80) or mass effect (n = 17). The aneurysms measured 5 cm +/- 2.8 mm; 68% were < or =5 mm. All patients were followed up clinically for an average of 54.5 +/- 20.9 months and radiologically with sequential digital subtraction angiography at 6 and 18 months. RESULTS: Total occlusion of the aneurysm was successfully achieved in 71.1% of patients after the initial treatment and in 82.5% after subsequent treatments. The retreatment rate was 17.5%. Procedure-related complication and mortality rates were 11.3% and 0%, respectively. The overall mortality was 5%, including mortality due to treatment failure in 1%. Neurologic outcomes were excellent in 77% of patients. Improved neurologic status, unchanged status, and deteriorated status was noted in 61.5%, 22%, and 16.5% of patients, respectively, at the end of the follow-up period. Intrinsic differences existed between Chinese and Western patients regarding the size of the aneurysm at presentation, periprocedural complications, and progression patterns of anatomic outcomes. CONCLUSION: Endovascular coiling with GDCs is a reasonably effective and safe treatment for intracranial aneurysms in this group of Hong Kong Chinese patients, with favorable clinical and radiologic outcomes.

Ruptured distal anterior choroidal artery aneurysm presenting with right intracerebral haematoma: clipping aided by subpial uncal resection.

This report describes a rare case of a distal right anterior choroidal artery aneurysm which developed a right intracerebral haematoma and intraventricular haemorrhage and was treated by surgical exploration and clipping with the aid of a limited subpial resection of the uncus and ambient gyrus. The technique of limited subpial uncal resection allows the surgeon to follow the anterior choroidal artery without much difficulty, achieves proximal control early and aids in the eventual clipping procedure.

A rare congenital anastomosis between the vertebral artery and internal carotid artery.

A case of congenital anastomosis between the vertebral artery and internal carotid artery is presented. This rare anomaly was an incidental finding at cerebral angiography in a patient with a suspected ruptured cerebral aneurysm with subarachnoid hemorrhage.