Unique experiences with intercontinental trials in stroke - part II.

Supported by the Canadian Medical Research Council we performed a randomized trial extending from Newfoundland to British Columbia. With others a number of observations showed that aspirin will reduce stroke. With National Institute of Neurological Disorders and Stroke support we learned who would benefit and not from surgery in these stroke threatened carotid diseased patients. We evaluated the upper limits of acceptability of complications beyond which harm was done. Amassing this large data base of approximately 5000 individuals, followed for five years, previously unknown carotid phenomena were observed: 1. Ischemic stroke occurs in patients with prolapsing mitral valves; 2. There is risk of stroke in patients with residual thrombi in the occluded stump of the carotid artery; 3. We detected a lower risk than expected in patients with nearly occluded carotid arteries. We support the contention of Yusuf and Cairns' that Canada needs to give more financial support to purely clinical research. It pays off !

Early minimally invasive intracerebral hemorrhage evacuation: a phase 2a feasibility, safety, and promise of surgical efficacy study.

BACKGROUND: Surgical treatment of intracerebral hemorrhage (ICH) is unproven, although meta-analyses suggest that both early conventional surgery with craniotomy and minimally invasive surgery (MIS) may be beneficial. We aimed to demonstrate the safety, feasibility, and promise of efficacy of early MIS for ICH using the Aurora Surgiscope and Evacuator. METHODS: We performed a prospective, single arm, phase IIa Simon's two stage design study at two stroke centers (10 patients with supratentorial ICH volumes ≥20 mL and National Institutes of Health Stroke Scale (NIHSS) score of ≥6, and surgery commencing <12 hours after onset). Positive outcome was defined as ≥50% 24 hour ICH volume reduction, with the safety outcome lack of significant ICH reaccumulation. RESULTS: From December 2019 to July 2020, we enrolled 10 patients at two Australian Comprehensive Stroke Centers, median age 70 years (IQR 65-74), NIHSS score 19 (IQR 19-29), ICH volume 59 mL (IQR 25-77), at a median of 227 min (IQR 175-377) post-onset. MIS was commenced at a median time of 531 min (IQR 437-628) post-onset, had a median duration of 98 min (IQR 77-110), with a median immediate postoperative hematoma evacuation of 70% (IQR 67-80%). A positive outcome was achieved in 5/5 first stage patients and in 4/5 second stage patients. One patient developed significant 24 hour ICH reaccumulation; otherwise, 24 hour stability was observed (median reduction 71% (IQR 61-80), 5/9 patients <15 mL residual). Three patients died, unrelated to surgery. There were no surgical safety concerns. At 6 months, the median modified Rankin Scale score was 4 (IQR 3-6) with 30% achieving a score of 0-3. CONCLUSION: In this study, early ICH MIS using the Aurora Surgiscope and Evacuator appeared to be feasible and safe, warranting further exploration. TRIAL REGISTRATION NUMBER: ACTRN12619001748101.

Does treatment of ruptured intracranial aneurysms within 24 hours improve clinical outcome?

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether treating ruptured intracranial aneurysms within 24 hours of subarachnoid hemorrhage improves clinical outcome. METHODS: An 11-year database of consecutive ruptured intracranial aneurysms treated with endovascular coiling or craniotomy and clipping was analyzed. Outcome was measured by the modified Rankin Scale at 6 months. Our policy is to treat all cases within 24 hours of subarachnoid hemorrhage. Treatment delays are due to nonclinical logistical factors. RESULTS: Two hundred thirty cases were coiled or clipped within 24 hours of subarachnoid hemorrhage and 229 at >24 hours. No difference in age, gender, smoking, family history of subarachnoid hemorrhage, aneurysm size, or aneurysm location was found between the groups. Poor World Federation of Neurological Surgeons clinical grade patients were overrepresented in the ultra-early group. Increasing age and higher World Federation of Neurological Surgeons clinical grade were predictors of poor outcome. Eight point zero percent (16 of 199) of cases treated within 24 hours of SAH (ultra-early) were dependent or dead at 6 months compared with 14.4% (30 of 209) of those treated at >24 hours post-SAH (delayed; (χ2, P0.044) [corrected]. A total of 3.5% of cases coiled within 24 hours were dependent or dead at 6 months compared with 12.5% of cases coiled at 1 to 3 days, an 82% relative risk reduction and a 10.2% absolute risk reduction (χ2, P=0.040). These groups did not differ in age, World Federation of Neurological Surgeons clinical grade, aneurysm size, or aneurysm location. CONCLUSIONS: Treatment of ruptured aneurysms within 24 hours is associated with improved clinical outcomes compared with treatment at >24 hours. The benefit is more pronounced for coiling than clipping.

A case of conus medullaris teratoma.

In this report, we present a case of an adult patient with a mature teratoma of the conus medullaris. The patient was a 29-year-old postpartum female patient who developed unexplained urinary retention. Lumbar spine magnetic resonance imaging (MRI) examination revealed an intradural partly enhancing mixed cystic and solid lesion with intralesional intrinsic T1 hyperintense components that were suppressed on fat suppressed sequences, inseparable from the conus medullaris. Surgical resection was performed and histopathology findings were consistent with a mature teratoma. The patient made a complete recovery.

Association of copeptin, a surrogate marker of arginine vasopressin, with cerebral vasospasm and delayed ischemic neurologic deficit after aneurysmal subarachnoid hemorrhage.

OBJECTIVEDelayed ischemic neurological deficit (DIND) is a leading cause of mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Arginine vasopressin (AVP) is a hormone released by the posterior pituitary. It is known to cause cerebral vasoconstriction and has been implicated in hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Direct measurement of AVP is limited by its short half-life. Copeptin, a cleavage product of the AVP precursor protein, was therefore used as a surrogate marker for AVP. This study aimed to investigate the temporal relationship between changes in copeptin concentrations and episodes of DIND and hyponatremia.METHODSCopeptin concentrations in cerebrospinal fluid were quantified using enzyme-linked immunosorbent assay in 19 patients: 10 patients with DIND, 6 patients without DIND (no-DIND), and 3 controls.RESULTSCopeptin concentrations were higher in DIND and no-DIND patients than in controls. In hyponatremic DIND patients, copeptin concentrations were higher compared with hyponatremic no-DIND patients. DIND was associated with a combination of decreasing sodium levels and increasing copeptin concentrations.CONCLUSIONSIncreased AVP may be the unifying factor explaining the co-occurrence of hyponatremia and DIND. Future studies are indicated to investigate this relationship and the therapeutic utility of AVP antagonists in the clinical setting.

How assessment drives learning in neurosurgical higher training.

UNLABELLED: Certifying the competence of neurosurgeons is a process of critical importance to the people of Australia and New Zealand. This process of certification occurs largely through the summative assessment of trainees involved in higher neurosurgical training. Assessment methods in higher training in neurosurgery vary widely between nations. However, there are no data about the 'utility' (validity, reliability, educational impact) of any national (or bi-national) neurosurgical training system. The utility of this process in Australia and New Zealand is difficult to study directly because of the small number of trainees and examiners involved in the certifying assessments. This study is aimed at providing indirect evidence of utility by studying a greater number of trainees and examiners during a formative assessment conducted at a training seminar in Neurosurgery in April 2005. AIM: To evaluate an essay examination for neurosurgical trainees for its validity, reliability and educational impact. METHODS: A short answer essay examination was undertaken by 59 trainees and corrected by up to nine examiners per part of question. The marking data were analysed. An evaluation questionnaire was answered by 48 trainees. Eight trainees who successfully passed the Fellowship examination who had also taken the short essay examination underwent a semi-structured interview. RESULTS: The essay examination was found to be neither reliable (generalisability coefficient of 0.56 if the essay paper had comprised 6 questions) nor valid. Furthermore, evidence suggests that such an examination may encourage a pursuit of declarative knowledge at the expense of competence in performing neurosurgery. CONCLUSION: This analysis is not directly applicable to the Fellowship examination itself. However, this study does suggest that the effect of assessment instruments upon neurosurgical trainees' learning strategies should be carefully considered.

Cerebral vasospasm and delayed ischaemic deficit following elective aneurysm clipping.

Although common after subarachnoid haemorrhage, cerebral vasospasm (CVS) and delayed ischaemic neurological deficit (DIND) rarely occur following elective clipping of unruptured aneurysms. The onset of this complication is variable and its pathophysiology is poorly understood. We report two patients with CVS associated with DIND following unruptured aneurysmal clipping. The literature is reviewed and the potential mechanisms in the context of patient presentations are discussed. A woman aged 53 and a man aged 70 were treated with elective clipping of unruptured middle cerebral artery aneurysms, the older patient also having an anterior communicating artery aneurysm clipped. The operations were uncomplicated with no intra-operative bleeding, no retraction, no contusion, no middle cerebral artery (MCA) temporary clipping, and no intra-operative rupture. Routine post-operative CT scan and CT angiogram showed that in both patients the aneurysms were excluded from the circulation and there was no perioperative subarachnoid blood. Both patients had no neurological deficit post-operatively, but on day 2 developed DIND and vasospasm of the MCA. Both patients had angiographic improvement with intra-arterial verapamil treatment. In one patient, this was done promptly and the patient made a complete recovery, but in the other, the diagnosis was delayed for more than 24hours and the patient had residual hemiparesis and dysphasia due to MCA territory infarction. CVS and DIND following treatment of unruptured aneurysms is a very rare event. However, clinicians should be vigilant as prompt diagnosis and management is required to minimise the risk of cerebral infarction and poor outcome.

Midbrain and thalamic haemorrhage as first presentation of intracerebral glioma.

A case of spontaneous intracerebral haemorrhage (midbrain and thalamic, with intraventricular extension) as the first presentation of an anaplastic astrocytoma is presented. Multiple CT scans and cerebral angiography failed to identify any vascular or neoplastic cause for the haemorrhage, and a presumptive diagnosis of hypertensive haemorrhage was made. Shunting of hydrocephalus was followed by early clinical improvement. However, delayed progressive deterioration necessitated MRI scan, which demonstrated a mass lesion in the basal ganglia and midbrain. This was subsequently found to be anaplastic astrocytoma on biopsy. The literature regarding this uncommon presentation of spontaneous intracerebral haemorrhage from an occult brain tumour is reviewed. The need for investigation and close follow-up of presumed hypertensive haemorrhage is emphasised by this case.

The neurosurgical training curriculum in Australia and New Zealand is changing. Why?

The Neurosurgical Advanced Training curriculum of the Royal Australasian College of Surgeons (RACS) is currently undergoing change. Given the high standard of neurosurgery in Australia and New Zealand, it may be questioned why such change is necessary. However, the curriculum has not kept pace with developments in professional practice, educational practice or educational theory, particularly in the assessment of medical competence and performance. The curriculum must also adapt to the changing training environment, particularly the effects of reduced working hours, reducing caseloads due to shorter inpatient hospital stays and restricted access to public hospital beds and operating theatres, and the effects of sub-specialisation. A formal review of the curriculum is timely.

Poor-grade aneurysmal subarachnoid hemorrhage: outcome after treatment with urgent surgery.

OBJECTIVE: We sought to determine whether the rebleeding rate in poor-grade patients justified a period of supportive observation before selective treatment and whether unselected ultraearly surgery would lead to acceptable results. METHODS: A prospectively audited, nonselected series of 177 consecutive poor-grade (i.e., World Federation of Neurological Surgeons Grades IV and V) patients with aneurysmal subarachnoid hemorrhage managed during a 9-year period was analyzed. A management policy of aggressive ultraearly surgery (not selected by age or by grade) was followed. Coiling was not available. Outcomes were assessed at 3 months. RESULTS: Despite the aggressive management policy, surgery could be performed in only 132 poor-grade patients (75%). Twenty percent of all patients were 70 years of age or older (15% of the surgical cases). All surgery was performed within 12 hours of subarachnoid hemorrhage (majority <6 h). Preoperative rebleeding occurred within the first 12 hours (>85% within 6 h) in 20% of the patients, which is four times the rate found in good-grade patients managed according to the same policy. Outcome assessment performed at 3 months in the 132 poor-grade surgical patients revealed that 40% were independent, 15% were dependent, and 45% had died. There was no significant difference in outcomes for young and old (70+ yr) poor-grade surgical patients (P > 0.05). CONCLUSION: The high ultraearly rebleeding rate indicates a need to urgently secure the ruptured aneurysm by performing surgery or coiling, and this indication is more pronounced for poor-grade patients than for good-grade patients. The outcome results of ultraearly surgery indicate that a nonselective policy does not lead to a large number of dependent survivors, even among elderly poor-grade patients.

Ultra-early surgery for aneurysmal subarachnoid hemorrhage: outcomes for a consecutive series of 391 patients not selected by grade or age.

OBJECT: This study was undertaken to determine the outcomes in an unselected group of patients treated with semiurgent surgical clipping of aneurysms following subarachnoid hemorrhage (SAH). METHODS: A clinical management outcome audit was conducted to determine outcomes in a group of 391 consecutive patients who were treated with a consistent policy of ultra-early surgery (all patients treated within 24 hours after SAH and 85% of them within 12 hours). All neurological grades were included, with 45% of patients having poor grades (World Federation of Neurosurgical Societies [WFNS] Grades IV and V). Patients were not selected on the basis of age; their ages ranged between 15 and 93 years and 19% were older than 70 years. The series included aneurysms located in both anterior and posterior circulations. Eighty-eight percent of all patients underwent surgery and only 2.5% of the series were selectively withdrawn (by family request) from the prescribed surgical treatment. In patients with good grades (WFNS Grades I-III) the 3-month postoperative outcomes were independence (good outcome) in 84% of cases, dependence (poor outcome) in 8% of cases, and death in 9%. In patients with poor grades the outcomes were independence in 40% of cases, dependence in 15% of cases, and death in 45%. There was a 12% rate of rebleeding with all cases of rebleeding occurring within the first 12 hours after SAH; however, outcomes of independence were achieved in 46% of cases in which rebleeding occurred (43% mortality rate). Rebleeding was more common in patients with poor grades (20% experienced rebleeding, whereas only 5% of patients with good grades experienced rebleeding). CONCLUSIONS: The major risk of rebleeding after SAH is present within the first 6 to 12 hours. This risk of ultra-early rebleeding is highest for patients with poor grades. Securing ruptured aneurysms by surgery or coil placement on an emergency basis for all patients with SAH has a strong rational argument.

Current intracerebral haemorrhage management.

Primary intracerebral haemorrhage (ICH) refers to spontaneous bleeding from intraparenchymal vessels. It accounts for 10-20% of all strokes, with higher incidence rates amongst African and Asian populations. The major risk factors are hypertension and age. In addition to focal neurological findings, patients may present with symptoms of elevated intracranial pressure. The diagnosis of ICH can only be made through neuro-imaging. A CT scan is presently standard, although MRI is increasingly important in the evaluation of acute cerebrovascular disease. A significant proportion of intracerebral haematomas expand in the first hours post-ictus and this is often associated with clinical worsening. There is evidence that the peri-haematomal region is compromised in ICH. This tissue is oedematous, although the precise pathogenesis is controversial. An association between elevated arterial pressure and haematoma expansion has been reported. Although current guidelines recommend conservative management of arterial pressure in ICH, an acute blood pressure lowering trial is overdue. ICH is associated with a high early mortality rate, although a significant number of survivors make a functional recovery. Current medical management is primarily aimed at prevention of complications including pneumonia and peripheral venous thromboembolism. Elevated intracranial pressure may be treated medically or surgically. Although the latter definitively lowers elevated intracranial pressure, the optimal patient selection criteria are not clear. Aggressive treatment of hypertension is essential in the primary and secondary prevention of ICH.

Aggressive surgical treatment of elderly patients following subarachnoid haemorrhage: management outcome results.

This report presents 74 consecutive cases of subarachnoid haemorrhage (SAH) in patients aged 70 years or older, compared with the 317 consecutive younger patients treated during the same period. An ultra-early surgical strategy for all SAH cases was used throughout the study period. Management outcome for all grades of elderly patients was independent in 38%, dependent in 14% and death in 49%. Surgical 3-month outcome of good grade elderly patients was independent 53%, dependent 19% and death 28%; and for poor grades was independent 35%, dependent 15% and death 50%. Elderly poor grade patients had similar outcome to younger patients, although good grade patients had better outcome in the younger group than the elderly group. Despite ultra-early surgery, rebleeding (<12 h of SAH) occurred in 9% of the elderly series. Aggressive, ultra-early treatment is likely to benefit elderly SAH patients, the potential benefit being greater for poor grade elderly patients.

Mycotic intracavernous carotid aneurysm.

Intracavernous carotid mycotic aneurysms are rare and management is dictated by clinical presentation. This case involved a patient presenting with a symptomatic expanding proximal internal carotid artery aneurysm treated with antibiotics and balloon occlusion but with thromboembolic complications resulting in a fatal outcome. Points of discussion include difficulties faced in reaching a diagnosis, management options for mycotic aneurysms and the rationale in this case for choosing endovascular rather than surgical treatment. The use and limitations of trial balloon occlusion are discussed as well as complications of vessel occlusion, in particular thromboembolism. Also discussed is the importance of surveillance imaging and the impact of sepsis on overall management.

Dural metastases mimicking meningioma. Case report and review of the literature.

The typical appearance of meningioma on CT and MRI is well known. Particularly in the elderly, the imaging appearance is sometimes considered diagnostic of these benign tumours without histopathological confirmation. However, other more aggressive neoplasms can present with a classical CT and MRI appearance of meningioma, indicating the need for histopathological confirmation wherever possible. We report a case of dural metastases which, on both pre-operative CT and MRI and at surgery, had the typical appearance of a falcine meningioma. Histopathology and immunohistochemistry revealed adenocarcinoma of renal cell origin, and the renal primary was identified on subsequent abdominal investigation. The literature regarding dural metastases is reviewed. To our knowledge, this is the first reported case of a renal carcinoma metastasizing directly to the dura. Although rare, dural metastases can mimic meningioma, and this needs to be considered if conservative therapy or radiosurgery are to be offered to a patient with radiological diagnosis of meningioma.

Acute atlanto-axial post-operative subluxation following posterior C1/2 fusion.

Two cases referred with acute post-operative C1/2 subluxation following posterior fusion are reported. Both cases had initial treatment for atlanto-axial instability with posterior cable (Brooks and interspinous) and graft techniques, and placed immediately in a Philadelphia collar. One case was found to have subluxed immediately post-operatively when failing to breathe following reversal of anaesthetic agents, and despite immediate realignment and reoperation was left with a significant quadriparesis. The other patient was noted to have subluxed on routine X-ray on day 4, and had no neurological deficit before or after reoperation. Risk factors for this dangerous complication are discussed and the techniques of C1/2 posterior fusion and stabilization are reviewed in detail. Surgeons performing atlanto-axial stabilization procedures should be familiar with and have expertize in the complete range of techniques described and choose the one most appropriate for the patient's individual requirements.

Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial.

CONTEXT: Prehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown. OBJECTIVE: To determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score, <9) and hypotensive (systolic blood pressure, <100 mm Hg). The patients were enrolled between December 14, 1998, and April 9, 2002, in Melbourne, Australia. INTERVENTIONS: Patients were randomly assigned to receive a rapid intravenous infusion of either 250 mL of 7.5% saline (n = 114) or 250 mL of Ringer's lactate solution (n = 115; controls) in addition to conventional intravenous fluid and resuscitation protocols administered by paramedics. Treatment allocation was concealed. MAIN OUTCOME MEASURE: Neurological function at 6 months, measured by the extended Glasgow Outcome Score (GOSE). RESULTS: Primary outcomes were obtained in 226 (99%) of 229 patients enrolled. Baseline characteristics of the groups were equivalent. At hospital admission, the mean serum sodium level was 149 mEq/L for HTS patients vs 141 mEq/L for controls (P<.001). The proportion of patients surviving to hospital discharge was similar in both groups (n = 63 [55%] for HTS group and n = 57 [50%] for controls; P =.32); at 6 months, survival rates were n = 62 (55%) in the HTS group and n = 53 (47%) in the control group (P =.23). At 6 months, the median (interquartile range) GOSE was 5 (3-6) in the HTS group vs 5 (5-6) in the control group (P =.45). There was no significant difference between the groups in favorable outcomes (moderate disability and good outcome survivors [GOSE of 5-8]) (risk ratio, 0.99; 95% confidence interval, 0.76-1.30; P =.96) or in any other measure of postinjury neurological function. CONCLUSION: In this study, patients with hypotension and severe TBI who received prehospital resuscitation with HTS had almost identical neurological function 6 months after injury as patients who received conventional fluid.