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.

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.

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.

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.

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 !

Comparison of microsurgery and endovascular treatment on clinical outcome following poor-grade subarachnoid hemorrhage.

Poor-grade (World Federation of Neurological Surgeons [WFNS] clinical grading scale grades IV and V) subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. However, the correlation between the timing, modality of intervention (clipping or coiling) and the clinical outcome is not clear. This study aims to examine this correlation. Patients presenting with WFNS grades IV and V aneurysmal SAH between 1997 and 2008 to a single centre were studied. An aggressive policy of early intervention was followed, and the selection of endovascular versus microsurgical intervention was made according to angiographic rather than clinical features. Clinical outcomes were graded using the modified Rankin scale (mRS) at 6 month follow-up. One hundred and forty-three poor-grade patients (23.9% of all 598 aneurysmal SAH patients) were studied. Treatment was microsurgical in 83 (58.0%) and endovascular in 60 (42%) patients. Twenty patients (14.0%) were lost to follow-up. Good outcome (mRS 0-2) at 6 months was found in 45 microsurgical patients (63.3%) and 24 endovascular patients (46.1%). This trend towards better clinical outcomes in the microsurgical group was not statistically significant. With an aggressive early treatment policy more than half of the poor-grade SAH patients demonstrated a good clinical outcome. Microsurgery and endovascular treatment, when selected primarily according to angiographic features, were equally likely to achieve good outcome.

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.

Risk of growth in unruptured intracranial aneurysms: a retrospective analysis.

This study sought to define the growth of unruptured intracranial aneurysms, in particular the frequency of growth and the characteristic factors predictive of growth. Two hundred and eight patients with 285 unruptured aneurysms were followed. Electronic records and angiographic films were obtained for measurements of aneurysm size. The mean follow-up duration was 21.8 months (range 1.1-137.3 months). Growth was identified in 95 of the 285 aneurysms (33.3%). The cumulative incidence of growth predicted using the Kaplan-Meier method was 22.7% at 1 year, 35.2% at 2 years, and 47.7% at 3 years. Aneurysm growth was significantly associated with a patient history of excessive alcohol consumption (p=0.04). A high incidence of growth can be seen in conservatively managed aneurysms with time. Consequently, continual follow-up is recommended to monitor for aneurysmal growth.

Gender differences in outcome in patients with hypotension and severe traumatic brain injury.

BACKGROUND: Animal studies have identified hormonal influences on responses to injury and recovery, creating a potential gender effect on outcome. Progesterone and oestrogen are thought to afford protection in the immediate post-injury period, suggesting females have an advantage, although there has been limited evidence of this in human outcome studies. METHODS: This study examined the influence of gender on outcome in 229 adults (151 males), aged >17 years, with severe blunt head trauma, initial GCS <9 and hypotension, recruited into a randomised controlled trial of pre-hospital hypertonic saline resuscitation versus conventional fluid management. Outcome was measured by survival and Glasgow Outcome Scale-Extended version (GOS-E) scores at 6 months post-injury. RESULTS: Females recruited into the study had a higher mean age. Females were more likely to be injured as passengers and pedestrians and males as drivers or motorcyclists. There were no gender differences in GCS or injury severity scores, ICP, cerebral perfusion pressure, gas exchange (PaO2/FiO2 ratio), or duration of mechanical ventilation. After controlling for GCS, age and cause of injury, females had a lower rate of survival. They also showed a lower rate of good outcome (GOS-E score >4) at 6 months, but this appeared to reflect the lower rate of initial survival. Those females surviving had similar outcomes to males. CONCLUSIONS: The study provides no evidence that females fare better than males following severe TBI, suggesting rather that females may fare worse.

Dysembryoplastic neuroepithelial tumor (DNT)-like oligodendrogliomas or Dnts evolving into oligodendrogliomas: two illustrative cases.

A review of dysembryoplastic neuroepithelial tumors (DNTs) in 14 patients over a 12-year period revealed four patients re-operated because of changes on magnetic resonance imaging (MRI) suggesting tumor recurrence or progression. In three of these, the histological features were identical to the initial DNT. In the fourth patient, persistent DNT was surrounded by WHO grade 2 oligoastrocytoma. In one of the other 10 patients, WHO grade 2 oligodendroglioma was present in white matter deep to and completely separate from a cortically based DNT. Fluorescence in situ hybridization showed codeletion of 1p and 19q in both the DNT and oligodendroglioma and oligoastrocytoma components. Deletions were not identified in any other tumor. Our findings corroborate other studies that 1p and 19q deletions are uncommon in DNT. These two unusual tumors also raise the possibility that rare DNTs may evolve into oligodendroglioma or oligoastrocytoma. DNTs with this altered biology can be identified by 1p and 19q deletion analysis.

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.

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.

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.