James V. Byrne

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.

Classical pituitary apoplexy : clinical features, management and outcome

The term classical pituitary apoplexy describes a clinical syndrome characterized by sudden headache, vomiting, visual impairment and meningismus caused by the rapid enlargement of a pituitary adenoma usually due to haemorrhagic infarction of the tumour. Most published reports looking at the clinical features and management of pituitary apoplexy have not differentiated between patients with clinical and subclinical apoplexy, the latter diagnosed at surgery. Furthermore, little is reported on the clinical outcome, in particular visual and endocrinological, and the role of radiotherapy. The purpose of this study was to observe not only the clinical presentation but also the possible predisposing events, investigations, management, clinical outcome as well as the role of radiotherapy in patients presenting with classical pituitary apoplexy.

Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study.

Introduction Flow diversion is a new approach to the endovascular treatment of intracranial aneurysms which uses a high density mesh stent to induce sac thrombosis. These devices have been designed for the treatment of complex shaped and large size aneurysms. So far published safety and efficacy data on this approach is sparse. Material and Methods Over 8 months, standardized clinical and angiographic data were collected on 70 patients treated with a flow diverter device (SILK flow diverter (SFD)) in 18 centres worldwide. Treatment and early follow up details were audited centrally. SFDs were deployed alone in 57 (81%) or with endosaccular coils in 10 (14%) aneurysms, which included: 44 (63%) saccular, 26 (37%) fusiform shapes and 18 (26%) small, 37 (53%) large, 15 (21%) giant sizes. Treatment outcome data up to 30 days were reported for all patients, with clinical (50 patients) and imaging (49 patients) follow up (median 119 days) data available. Results Difficulties in SFD deployment were reported in 15 (21%) and parent artery thrombosis in 8 (11%) procedures. Procedural complications caused stroke in 1 and serious extracranial bleeding in 3 patients; 2 of whom developed fatal pneumonias. Delayed worsening of symptoms occurred in 5 patients (3 transient, 1 permanent neurological deficit, and 1 death) and fatal aneurysm bleeding in 1 patient. Overall permanent morbidity rates were 2 (4%) and mortality 4 (8%). Statistical analysis revealed no significant association between complications and variables related to treated aneurysm morphology or rupture status. Conclusion This series is the largest reporting outcome of the new treatment approach and provides data for future study design. Procedural difficulties in SFD deployment were frequent and anti-thrombosis prophylaxis appears to reduce the resulting clinical sequelae, but at the cost of morbidity due to extracranial bleeding. Delayed morbidity appears to be a consequence of the new approach and warrants care in selecting patients for treatment and future larger studies.

Genome-wide association study of intracranial aneurysm identifies three new risk loci

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with ∼832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10−12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10−9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10−9). We also confirmed prior associations near SOX17 (8q11.23–q12.1; OR = 1.28, P = 1.3 × 10−12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10−22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Intensity-based 2-D - 3-D registration of cerebral angiograms

We propose a new method for aligning three-dimensional (3-D) magnetic resonance angiography (MRA) with 2-D X-ray digital subtraction angiograms (DSA). Our method is developed from our algorithm to register computed tomography volumes to X-ray images based on intensity matching of digitally reconstructed radiographs (DRRs). To make the DSA and DRR more similar, we transform the MRA images to images of the vasculature and set to zero the contralateral side of the MRA to that imaged with DSA. We initialize the search for a match on a user defined circular region of interest. We have tested six similarity measures using both unsegmented MRA and three segmentation variants of the MRA. Registrations were carried out on images of a physical neuro-vascular phantom and images obtained during four neuro-vascular interventions. The most accurate and robust registrations were obtained using the pattern intensity, gradient difference, and gradient correlation similarity measures, when used in conjunction with the most sophisticated MRA segmentations. Using these measures, 95% of the phantom start positions and 82% of the clinical start positions were successfully registered. The lowest root mean square reprojection errors were 1.3 mm (standard deviation 0.6) for the phantom and 1.5 mm (standard deviation 0.9) for the clinical data sets. Finally, we present a novel method for the comparison of similarity measure performance using a technique borrowed from receiver operator characteristic analysis.

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.

What is the natural history of nonoperated nonfunctioning pituitary adenomas

Background  Series of patients systematically investigating the outcome of clinically nonfunctioning pituitary adenomas (NFAs) not treated by surgery or radiotherapy during long follow‐up periods are limited. Most reports involve the follow‐up of selected cases of incidentally found lesions, rendering their results unreliable on the assessment of the pros and cons of a ‘watch and wait’ policy.

Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotide

Background  Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case.

Technical Feasibility and Application of Mechanical Thrombectomy with the Solitaire FR Revascularization Device in Acute Basilar Artery Occlusion

BACKGROUND AND PURPOSE: Acute BAO is a devastating neurological condition associated with a poor clinical outcome and a high mortality rate. Recanalization has been identified as a major prognostic factor for good outcome in BAO. Mechanical thrombectomy using retrievable stents is an emerging treatment option for acute stroke. First clinical trials using stent retrievers have shown promising high recanalization rates. However, these studies mainly included large artery occlusions in the anterior circulation with only a few or single cases of BAO. Therefore, the purpose of this study was to evaluate technical feasibility, safety, and efficacy of mechanical thrombectomy using retrievable stent in the treatment of acute BAO. MATERIALS AND METHODS: Fourteen consecutive patients with BAO undergoing endovascular therapy using retrievable stents (Solitaire FR Revascularization Device) were included. Additional multimodal treatment approaches included thromboaspiration, intravenous and/or intra-arterial thrombolysis, and PTA/ permanent stent placement. Recanalization rates after multimodal therapy and stent retrieval were determined. Clinical outcome and mortality were assessed 3 months after treatment. RESULTS: Median patient age was 64.5 years (range 55–85). Median NIHSS score at presentation was 21 (range 5–36). Overall, successful recanalization (TICI 3 or 2b) was achieved in all patients (TICI 3 in 78.6%, 11/14). In 4 patients (28.6%), insufficient recanalization after stent retrieval was due to an underlying atherosclerotic stenosis. Additional deployment of a permanent intracranial stent was performed in 3 patients (21.4%) and PTA alone in 1 patient (7.1%), resulting in final TICI 3 in 1 patient and TICI 2b in 3 patients. Stent retrieval alone was performed in 4 patients (28.6%). Average number of device passes was 1.3 (range 1–3). Median procedure time to maximal recanalization was 47 minutes (range 10–252). No device-related complications or thromboembolic occlusion of a previously unaffected artery occurred. There was no symptomatic intracranial hemorrhage. At 3 months, good functional outcome (mRS 0–2) was observed in 28.6% (4/14); overall mortality was 35.7% (5/14). CONCLUSIONS: A multimodal endovascular approach using retrievable stents in BAO has high recanalization rates, with very low complication rates. Underlying atherothrombotic stenotic lesions of the basilar artery may still necessitate additional permanent stent placement to achieve complete recanalization.

Determinants of left ventricular mass in obesity; a cardiovascular magnetic resonance study

BackgroundObesity is linked to increased left ventricular mass, an independent predictor of mortality. As a result of this, understanding the determinants of left ventricular mass in the setting of obesity has both therapeutic and prognostic implications. Using cardiovascular magnetic resonance our goal was to elucidate the main predictors of left ventricular mass in severely obese subjects free of additional cardiovascular risk factors.Methods38 obese (BMI 37.8 ± 6.9 kg/m2) and 16 normal weight controls subjects, (BMI 21.7 ± 1.8 kg/m2), all without cardiovascular risk factors, underwent cardiovascular magnetic resonance imaging to assess left ventricular mass, left ventricular volumes and visceral fat mass. Left ventricular mass was then compared to serum and anthropometric markers of obesity linked to left ventricular mass, i.e. height, age, blood pressure, total fat mass, visceral fat mass, lean mass, serum leptin and fasting insulin level.ResultsAs expected, obesity was associated with significantly increased left ventricular mass (126 ± 27 vs 90 ± 20 g; p < 0.001). Stepwise multiple regression analysis showed that over 75% of the cross sectional variation in left ventricular mass can be explained by lean body mass (β = 0.51, p < 0.001), LV stroke volume (β = 0.31 p = 0.001) and abdominal visceral fat mass (β = 0.20, p = 0.02), all of which showed highly significant independent associations with left ventricular mass (overall R2 = 0.77).ConclusionThe left ventricular hypertrophic response to obesity in the absence of additional cardiovascular risk factors is mainly attributable to increases in lean body mass, LV stroke volume and visceral fat mass. In view of the well documented link between obesity, left ventricular hypertrophy and mortality, these findings have potentially important prognostic and therapeutic implications for primary and secondary prevention.