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Andrew J. Molyneux, David W. Ellison, James Morris and James V. Byrne

✓ The authors report the pathological and histological findings in two patients with giant partially thrombosed aneurysms who were treated by means of Guglielmi detachable coils with subtotal occlusion of the aneurysms. Autopsies of these patients were performed 2 and 6 months after endovascular treatment. The histological findings revealed coils embedded in largely unorganized thrombus in the aneurysms; there was no clear reduction in size of the aneurysms over the period. There was no evidence of endothelialization of the aneurysm neck demonstrated in either case. The significance of these findings is discussed.

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Andrew J. Molyneux and Stuart C. Coley

✓ In this paper the authors describe the first use of a new liquid embolic agent (Onyx) to treat spinal cord arteriovenous malformations (AVMs). Because its properties make it more predictable to use than currently available liquid agents, the authors believe that this material has great potential in the endovascular management of both spinal cord and brain AVMs. This very promising agent merits further clinical study.

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Yvonne Hart, Mary Sneade, Jacqueline Birks, Joan Rischmiller, Richard Kerr and Andrew Molyneux

Object

The aim of this study was to determine the probability of seizures after treatment of a ruptured cerebral aneurysm by clip occlusion and coil embolization, and to identify the risks and predictors of seizures over the shortand long-term follow-up period.

Methods

The study population included 2143 patients with ruptured intracranial aneurysms who were enrolled in 43 centers and randomly assigned to clip application or coil placement. Those patients suffering a seizure were identified prospectively at various time points after randomization, as follows: before treatment; after treatment and before discharge; after discharge to 1 year; and annually thereafter.

Results

Two hundred thirty-five (10.9%) of the 2143 patients suffered a seizure after randomization; 89 (8.3%) of 1073 and 146 (13.6%) of 1070 in the endovascular and neurosurgical allocations, respectively (p = 0.014). In 19 patients the seizure was associated with a rehemorrhage. Of those patients who underwent coil placement alone, without additional procedures, 52 suffered a seizure, and in the group with clip occlusion alone, 91 patients suffered a seizure.

The risk of a seizure after discharge in the endovascular group was 3.3% at 1 year and 6.4% at 5 years. In the neurosurgical group it was 5.2% at 1 year and 9.6% at 5 years. The risk of seizure was significantly greater in the neurosurgical group at both 2 years and at up to 14 years (p = 0.005 and p = 0.013, respectively). The significant predictors of increased risk were as follows: neurosurgical treatment allocation, hazard ratio (HR) 1.64 (95% CI 1.19–2.26); younger age, HR 1.54 (95% CI 1.14–2.13); Fisher grade > 1 on CT scans, HR 1.34 (95% CI 0.62–2.87); delayed ischemic neurological deficit due to vasospasm, HR 2.10 (95% CI 1.49–2.94); and thromboembolic complication, HR 5.08 (95% CI 3.00–8.61). A middle cerebral artery (MCA) aneurysm location was also a significant predictor of increased risk in both groups; the HR was 2.23 (95% CI 1.57–3.17), with the probability of seizure at 6.1% and 11.5% at 1 year in the endovascular and neurosurgery groups, respectively.

Conclusions

The risk of seizures after coil embolization is significantly lower than that after clip occlusion. An MCA aneurysm location increased the risk of seizures in both groups.

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James V. Byrne, Min-Joo Sohn, Andrew J. Molyneux and B. Chir

Object

During a 5-year period 317 patients presenting with aneurysmal subarachnoid hemorrhage were successfully treated by coil embolization within 30 days of hemorrhage. The authors followed these cases to assess the stability of aneurysm occlusion and its longer-term efficacy in protecting patients against rebleeding.

Methods

These cases were followed for 6 to 65 months (median 22.3 months) by clinical review, angiography performed at 6 months posttreatment, and annual postal questionnaires.

Conclusions

Stable angiographic occlusion was evident in 86.4% of small and 85.2% of large aneurysms with recurrent filling in 38 (14.7%) of 259 aneurysms. Rebleeding was caused by aneurysm recurrence in four patients (between 11 and 35 months posttreatment) and by rupture of a coincidental untreated aneurysm in one patient. Annual rebleeding rates were 0.8% in the 1st year, 0.6% in the 2nd year, and 2.4% in the 3rd year after aneurysm embolization, with no rebleeding in subsequent years. Rebleeding occurred in three (7.9%) of 38 recurrent aneurysms and in one (0.4%) of 221 aneurysms that appeared stable on angiography. Periodic follow-up angiography after coil embolization is recommended to identify aneurysm recurrence and those patients at a high risk of late rebleeding.

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Toqir K. Mukhtar, Andrew J. Molyneux, Nick Hall, David R. G. Yeates, Raphael Goldacre, Mary Sneade, Alison Clarke and Michael J. Goldacre

OBJECTIVE

In this study, the authors examined trends in population-based hospital admission rates, patient-level case fatality rates (CFRs), and population-based mortality rates for nontraumatic (spontaneous) subarachnoid hemorrhage (SAH) in England.

METHODS

Population-based admission and mortality data (59,599 people admitted to a hospital with SAH, 1999–2010; 37,836 people whose death certificates mentioned SAH, 1995–2010) were analyzed.

RESULTS

Hospital admission rates for SAH per million population declined by 18.3%, from 100.4 (95% CI 97.6−103.1) in 1999 to 82.0 (95% CI 79.7−84.4) in 2010. CFRs at less than 30 days per 100 patients decreased by 18.2%, from 29.7 (95% CI 28.5−31.0) in 1999 to 24.3 (95% CI 23.2−25.5) in 2010. Population-based mortality rates per million population, where SAH was recorded as underlying cause of death on the death certificate, declined by 39.8%, from 41.2 (95% CI 39.5−43.0) in 1999 to 24.8 (95% CI 23.6−26.1) in 2010.

CONCLUSIONS

Population-based hospital admission rates, patient-level CFRs, and population-based mortality rates all declined between 1999 and 2010. Part of the decline in mortality rates for SAH is likely to be attributable to a decline in incidence. It is also, in part, attributable to increased survival after SAH. The available data do not allow us to compare the effects of different treatment methods for SAH on case fatality and mortality. During the period of study, mortality rates declined by almost 40%, and it is likely that there are a number of factors contributing to this substantial improvement in outcomes for SAH patients in England.

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Don Ilodigwe, M. Stat., Gordon D. Murray, Neal F. Kassell, James Torner, Richard S. C. Kerr, Andrew J. Molyneux and R. Loch Macdonald

Object

In randomized clinical trials of subarachnoid hemorrhage (SAH) in which the primary clinical outcomes are ordinal, it has been common practice to dichotomize the ordinal outcome scale into favorable versus unfavorable outcome. Using this strategy may increase sample sizes by reducing statistical power. Authors of the present study used SAH clinical trial data to determine if a sliding dichotomy would improve statistical power.

Methods

Available individual patient data from tirilazad (3552 patients), clazosentan (the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage trial [CONSCIOUS-1], 413 patients), and subarachnoid aneurysm trials (the International Subarachnoid Aneurysm Trial [ISAT], 2089 patients) were analyzed. Treatment effect sizes were examined using conventional fixed dichotomy, sliding dichotomy (logical or median split methods), or proportional odds modeling. Whether sliding dichotomy affected the difference in outcomes between the several age and neurological grade groups was also evaluated.

Results

In the tirilazad data, there was no significant effect of treatment on outcome (fixed dichotomy: OR = 0.92, 95% CI 0.80–1.07; and sliding dichotomy: OR = 1.02, 95% CI 0.87–1.19). Sliding dichotomy reversed and increased the difference in outcome in favor of the placebo over clazosentan (fixed dichotomy: OR = 1.06, 95% CI 0.65–1.74; and sliding dichotomy: OR = 0.85, 95% CI 0.52–1.39). In the ISAT data, sliding dichotomy produced identical odds ratios compared with fixed dichotomy (fixed dichotomy vs sliding dichotomy, respectively: OR = 0.67, 95% CI 0.55–0.82 vs OR = 0.67, 95% CI 0.53–0.85). When considering the tirilazad and CONSCIOUS-1 groups based on age or World Federation of Neurosurgical Societies grade, no consistent effects of sliding dichotomy compared with fixed dichotomy were observed.

Conclusions

There were differences among fixed dichotomy, sliding dichotomy, and proportional odds models in the magnitude and precision of odds ratios, but these differences were not as substantial as those seen when these methods were used in other conditions such as head injury. This finding suggests the need for different outcome scales for SAH.

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Rufus A. Corkill, Aristotelis P. Mitsos and Andrew J. Molyneux

Object

The aim of this study was to analyze the endovascular treatment results of using the Onyx liquid embolic system for spinal intramedullary arteriovenous malformations (AVMs).

Methods

The clinical and radiological records of 17 patients with symptomatic spinal intramedullary AVMs treated exclusively by embolization with Onyx between 1999 and 2003 were retrospectively reviewed. There were 12 females and five males in the patient series (mean age 29 years). Four of these AVMs were located in the cervical spine, eight in the thoracic spine, and five in the lumbar spine. The clinical presentation of these AVMs included upper motor neuron signs and symptoms, and hemorrhage was the initial presentation in 12 patients. Neurological and functional evaluation was performed before and after treatment with Onyx in all patients.

Results

Thirteen patients underwent a single endovascular treatment and four patients underwent two endovascular treatments (average 1.23 sessions per patient). Intraprocedural complications occurred on two occasions without neurological consequences. The mean follow-up duration was 24.3 months. Angiographic outcomes included total AVM obliteration in six patients (37.5%), subtotal obliteration in five patients (31.25%), and partial obliteration in five patients (31.25%). Improvement in neurological and/or functional status was noted in 14 patients, resulting in an 82% rate of overall good clinical outcome.

Conclusions

Embolization using the Onyx system is a promising treatment method for spinal vascular malformations, even for challenging intramedullary AVMs. Larger studies with longer follow-up durations will further enhance our knowledge on the safety and efficacy of this relatively new liquid embolic agent.