Andrew Molyneux

International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.

BACKGROUND Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments. METHODS We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol. FINDINGS 190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6% (95% CI 8.9-34.2) and 6.9% (2.5-11.3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively. INTERPRETATION In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.

International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion

BACKGROUND Two types of treatment are being used for patients with ruptured intracranial aneurysms: endovascular detachable-coil treatment or craniotomy and clipping. We undertook a randomised, multicentre trial to compare these treatments in patients who were suitable for either treatment because the relative safety and efficacy of these approaches had not been established. Here we present clinical outcomes 1 year after treatment. METHODS 2143 patients with ruptured intracranial aneurysms, who were admitted to 42 neurosurgical centres, mainly in the UK and Europe, took part in the trial. They were randomly assigned to neurosurgical clipping (n=1070) or endovascular coiling (n=1073). The primary outcome was death or dependence at 1 year (defined by a modified Rankin scale of 3-6). Secondary outcomes included rebleeding from the treated aneurysm and risk of seizures. Long-term follow up continues. Analysis was in accordance with the randomised treatment. FINDINGS We report the 1-year outcomes for 1063 of 1073 patients allocated to endovascular treatment, and 1055 of 1070 patients allocated to neurosurgical treatment. 250 (23.5%) of 1063 patients allocated to endovascular treatment were dead or dependent at 1 year, compared with 326 (30.9%) of 1055 patients allocated to neurosurgery, an absolute risk reduction of 7.4% (95% CI 3.6-11.2, p=0.0001). The early survival advantage was maintained for up to 7 years and was significant (log rank p=0.03). The risk of epilepsy was substantially lower in patients allocated to endovascular treatment, but the risk of late rebleeding was higher. INTERPRETATION In patients with ruptured intracranial aneurysms suitable for both treatments, endovascular coiling is more likely to result in independent survival at 1 year than neurosurgical clipping; the survival benefit continues for at least 7 years. The risk of late rebleeding is low, but is more common after endovascular coiling than after neurosurgical clipping.

A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981-86. 1. Methodology, demography and incident cases of first-ever stroke.

A prospective study of acute cerebrovascular disease in a community of about 105,000 people is reported. The study protocol combined rapid clinical assessment of patients with accurate diagnosis of the pathological type of stroke by CT or necropsy, whether or not they were admitted to hospital. The study population was defined as those people who were registered with one of 50 collaborating general practitioners (GPs). Referrals to the study were primarily from the GPs though, to ensure complete case ascertainment, hospital casualty and admission registers, death certificates and special data from the Oxford Record Linkage Study were also scrutinized. Six hundred and seventy five cases of clinically definite first-ever in a lifetime stroke were registered in four years yielding a crude annual incidence of 1.60/1,000 or 2.00/1,000 when adjusted to the 1981 population of England and Wales. The age and sex specific incidence rates for first stroke showed a steep rise with age for both sexes. The odds of a male sustaining a first stroke were 26% greater than those of a female. Ninety one per cent of patients were examined in a median time of four days after the event by a study neurologist and 88% had cerebral CT or necropsy.

Retreatment of Ruptured Cerebral Aneurysms in Patients Randomized by Coiling or Clipping in the International Subarachnoid Aneurysm Trial (ISAT)

Background and Purpose— Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence. Methods— Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model. Results— Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%) patients were retreated early and 9 (0.85%) late, 3 (0.3%) after rebleeding and 6 (0.6%) without. The mean time to late retreatment was 5.7 months. The hazard ratio (HR) for retreatment after EVT was 6.9 (95% CI=3.4 to 14.1) after adjustment for age (P=0.001, HR=0.97, 95% CI=0.95 to 0.98), lumen size (P=0.006, HR=1.1, 95% CI=1.03 to 1.18), and incomplete occlusion (P<0.001, HR=7.6, 95% CI=3.3 to 17.5). Conclusions— Late retreatment was 6.9 times more likely after EVT. Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT. After neurosurgical clipping, retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period. Short-term follow-up imaging is therefore insufficient to detect recurrences after EVT.

The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT)

Summary Background Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. At 1 year there was a 7% absolute and a 24% relative risk reduction of death and dependency in the coiling group compared with the clipping group, but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling. We report the long-term follow-up of patients in this UK cohort. Methods In ISAT, patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage, assuming treatment equipoise, between Sept 12, 1994, and May 1, 2002. We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0–18·5 years. We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires. Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records. The Office for National Statistics supplied data on deaths. This study is registered, number ISRCTN49866681. Findings At 10 years, 674 (83%) of 809 patients allocated endovascular coiling and 657 (79%) of 835 patients allocated neurosurgical clipping were alive (odds ratio [OR] 1·35, 95% CI 1·06–1·73). Of 1003 individuals who returned a questionnaire at 10 years, 435 (82%) patients treated with endovascular coiling and 370 (78%) patients treated with neurosurgical clipping were independent (modified Rankin scale score 0–2; OR 1·25; 95% CI 0·92–1·71). Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group (OR 1·34, 95% CI 1·07–1·67). 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage (17 from the target aneurysm). Interpretation Although rates of increased dependency alone did not differ between groups, the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group. Rebleeding was more likely after endovascular coiling than after neurosurgical clipping, but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years. Funding UK Medical Research Council.

Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. Methods— Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results— Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment.

Complications of cerebral angiography for patients with mild carotid territory ischaemia being considered for carotid endarterectomy.

It is essential to image the carotid bifurcation adequately in patients with symptomatic carotid territory ischaemia if they are being considered for carotid endarterectomy. Optimal resolution is achieved by selective intraarterial contrast angiography which is an invasive procedure carrying some risk. The overall risk-benefit of carotid endarterectomy is currently being investigated in several large randomised trials in Europe and North America. Because cerebral angiography is a prerequisite for carotid endarterectomy, the risks of cerebral angiography will need to be added to those of surgery when considering whether carotid endarterectomy is effective in the management of these patients. This study evaluated prospectively 382 patients with symptomatically mild carotid ischaemia who had cerebral angiography to visualise a potentially resectable lesion at the carotid bifurcation. Complications followed 14 cerebral angiograms in 13 patients (3.4%); two complications were local (0.5%), two systemic (0.5%) and 10 were neurological (2.6%). The neurological complications were transient (TIA 1, generalised seizure 1) in two patients (0.5%), reversible (stroke) in three (0.8%) and permanent (stroke) in five patients (1.3%). There were no deaths. The significant risk factors for post angiographic stroke were (1) stroke before angiography compared with transient ischaemic attacks of the eye or brain and (2) the presence of greater than or equal to 50% diameter stenosis of the symptomatic internal carotid artery; unfortunately it may be the latter patients who are most at risk of stroke as part of the natural history of their disease and therefore most in need of prophylactic carotid endarterectomy (which requires cerebral angiography). The absolute risk of post-angiographic stroke of patients for cerebral angiography using clinical evaluation and Duplex carotid ultrasound screening.

Recommendations for the Endovascular Treatment of Intracranial Aneurysms A Statement for Healthcare Professionals from the Committee on Cerebrovascular Imaging of the American Heart Association Council on Cardiovascular Radiology

Intracranial aneurysms are common, with a prevalence of 0.5% to 6% in adults, according to angiography and autopsy studies.1 Most intracranial aneurysms are asymptomatic and are never detected. Some are discovered incidentally in neuroimaging studies and some produce symptoms due to compression of neighboring nerves or adjacent brain tissue. Others are detected only after they have ruptured and caused subarachnoid hemorrhage, a devastating type of stroke asso-ciated with 32% to 67% case fatality and 10% to 20% long-term dependence in survivors due to brain damage.2 To prevent subarachnoid hemorrhage, physicians have developed methods to treat aneurysms. For ruptured aneurysms, early treatment within 24 to 72 hours has been recommended because the risk of subsequent rupture is high, with approximately 20% risk of rerupture in the first 2 weeks after subarachnoid hemorrhage.3 Each additional rupture substantially increases the risk of mortality and morbidity. Treatment has also been recommended for most unruptured aneurysms,4 although there is uncertainty about treatment of some small aneurysms <10 mm because their risk of rupture appears low.5,6⇓ The American Heart Association formed this special writing group to summarize the literature and create recommendations on endovascular therapy of ruptured and unruptured intracranial aneurysms. This statement is meant to extend previous statements on treatment of subarachnoid hemorrhage3 and on treatment of unruptured aneurysms.4 During the review, it became evident that any recommendations would be based primarily on expert opinion weighing evidence only from nonrandomized cohort studies and case series. In 1937, Walter Dandy reported the first successful surgical clipping of the neck of an aneurysm. Microsurgical techniques have steadily evolved since then, with development of a variety of surgical approaches and metal aneurysm clips. Repair of aneurysms in nearly all intracranial locations is possible by placing a clip made from a …

International Subarachnoid Aneurysm Trial of Neurosurgical Clipping Versus Endovascular Coiling. Subgroup Analysis of 278 Elderly Patients

Background and Purpose— It is often thought that elderly patients in particular would benefit from endovascular aneurysm treatment. The aim of this analysis was therefore to compare the efficacy and safety of endovascular coiling (EVT) with neurosurgical clipping (NST) in the subgroup of elderly SAH patients in the International Subarachnoid Aneurysm Trial (ISAT). Methods— In the ISAT cohort 278 SAH patients, 65 years or older, were enrolled. The patients were randomly allocated EVT (n=138) or NST (n=140). The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 (independent survival) at 1 year after the SAH. The rates of procedural complications and adverse events were also recorded. Results— 83 of 138 (60.1%) patients allocated EVT were independent compared to 78 of 140 (56.1%) allocated NST (N.S.). 36 of 50 (72.0%) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 (52.0%) allocated NST (P<0.05). 10 of 22 (45.5%) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 (86.7%) allocated NST (P<0.05). The epilepsy frequency was 0.7% in the EVT group compared to 12.9% in the NST group (P<0.001). Conclusions— In good grade elderly SAH patients with small anterior circulation aneurysms, EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms, whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST. EVT resulted in a lower epilepsy frequency than NST.

Embolisation of recently ruptured intracranial aneurysms.

Patients with subarachnoid haemorrhage due to the rupture of aneurysms unsuitable for craniotomy and clipping have been treated by coil embolisation within three weeks. Sixty nine of 75 consecutive patients were successfully treated. Procedure related complications occurred in 10 patients, resulting in permanent neurological deficits in three and one death (4.8%). The Glasgow outcome scores at six weeks were 53 grade 1, seven grade 2, four grade 3, and five grade 5. These results are comparable with surgical series despite a high proportion of aneurysms in the posterior cerebral circulation.