HydroCoils Are Associated with Lower Angiographic Recurrence Rates Than Are Bare Platinum Coils in Treatment of "Difficult-to-Treat" Aneurysms: A Post Hoc Subgroup Analysis of the HELPS Trial.

BACKGROUND AND PURPOSE: The HydroCoil Endovascular Aneurysm Occlusion and Packing Study was a randomized controlled trial that compared HydroCoils to bare platinum coils. Using data from this trial, we performed a subgroup analysis of angiographic and clinical outcomes of patients with "difficult-to-treat" aneurysms, defined as irregularly shaped and/or having a dome-to-neck ratio of <1.5. MATERIALS AND METHODS: Separate subgroup analyses comparing outcomes of treatment with HydroCoils to that of bare platinum coils were performed for the following: 1) irregularly shaped aneurysms, 2) regularly shaped aneurysms, 3) aneurysms with a dome-to-neck ratio of <1.5, and 4) aneurysms with a dome-to-neck ratio of ≥1.5. For each subgroup analysis, the following outcomes were studied at the last follow-up (3-18 months): 1) any recurrence, 2) major recurrence, 3) re-treatment, and 4) an mRS score of ≤2. Multivariate logistic regression analysis was performed to determine if the HydroCoil was independently associated with improved outcomes in these subgroups. RESULTS: Among the patients with an irregularly shaped aneurysm, the HydroCoil was associated with lower major recurrence rates than the bare platinum coils (17 of 66 [26%] vs 30 of 69 [44%], respectively; P = .046). Among the patients with an aneurysm with a small dome-to-neck ratio, the HydroCoil was associated with lower major recurrence rates than the bare platinum coils (18 of 73 [24.7%] vs 32 of 76 [42.1%], respectively; P = .02). No difference in major recurrence was seen between HydroCoils and bare platinum coils for regularly shaped aneurysms (42 of 152 [27.6%] vs 52 of 162 [32.1%], respectively; P = .39) or aneurysms with a large dome-to-neck ratio (41 of 145 [28.3%] vs 50 of 155 [32.3%], respectively; P = .53). CONCLUSIONS: This unplanned post hoc subgroup analysis found that HydroCoils are associated with improved angiographic outcomes in the treatment of irregularly shaped aneurysms and aneurysms with a dome-to-neck ratio of <1.5. Because this was a post hoc analysis, these results are not reliable and absolutely should not alter clinical practice but, rather, may inform the design of future randomized controlled trials.

Treatment of poor-grade subarachnoid hemorrhage trial.

BACKGROUND AND PURPOSE: Management of poor-grade subarachnoid hemorrhage is based on limited evidence from small single-center retrospective observational studies. The purpose of this study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients. MATERIALS AND METHODS: Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed. RESULTS: Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm (n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%. CONCLUSIONS: This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies.

Chemical dissection of the cell cycle: probes for cell biology and anti-cancer drug development.

Cancer cell proliferation relies on the ability of cancer cells to grow, transition through the cell cycle, and divide. To identify novel chemical probes for dissecting the mechanisms governing cell cycle progression and cell division, and for developing new anti-cancer therapeutics, we developed and performed a novel cancer cell-based high-throughput chemical screen for cell cycle modulators. This approach identified novel G1, S, G2, and M-phase specific inhibitors with drug-like properties and diverse chemotypes likely targeting a broad array of processes. We further characterized the M-phase inhibitors and highlight the most potent M-phase inhibitor MI-181, which targets tubulin, inhibits tubulin polymerization, activates the spindle assembly checkpoint, arrests cells in mitosis, and triggers a fast apoptotic cell death. Importantly, MI-181 has broad anti-cancer activity, especially against BRAF(V600E) melanomas.

Bioactive versus bare platinum coils in the treatment of intracranial aneurysms: the MAPS (Matrix and Platinum Science) trial.

BACKGROUND AND PURPOSE: The ability of polymer-modified coils to promote stable aneurysm occlusion after endovascular treatment is not well-documented. Angiographic aneurysm recurrence is widely used as a surrogate for treatment failure, but studies documenting the correlation of angiographic recurrence with clinical failure are limited. This trial compares the effectiveness of Matrix(2) polyglycolic/polylactic acid biopolymer-modified coils with bare metal coils and correlates the angiographic findings with clinical failure (ie, target aneurysm recurrence), a composite end point that includes any incident of posttreatment aneurysm rupture, retreatment, or unexplained death. MATERIALS AND METHODS: This was a multicenter randomized noninferiority trial with blinded end point adjudication. We enrolled 626 patients, divided between Matrix(2) and bare metal coil groups. The primary outcome was target aneurysm recurrence at 12 ± 3 months. RESULTS: At 455 days, at least 1 target aneurysm recurrence event had occurred in 14.6% of patients treated with bare metal coils and 13.3% of Matrix(2) (P = .76, log-rank test) patients; 92.8% of target aneurysm recurrence events were re-interventions for aneurysms that had not bled after treatment, and 5.8% of target aneurysm recurrence events resulted from hemorrhage or rehemorrhage, with or without retreatment. Symptomatic re-intervention occurred in only 4 (0.6%) patients. At 455 days, 95.8% of patients with unruptured aneurysms and 90.4% of those with ruptured aneurysms were independent (mRS ≤ 2). Target aneurysm recurrence was associated with incomplete initial angiographic aneurysm obliteration, presentation with rupture, and a larger aneurysmal dome and neck size. CONCLUSIONS: Tested Matrix(2) coils were not inferior to bare metal coils. Endovascular coiling of intracranial aneurysms was safe, and the rate of technical success was high. Target aneurysm recurrence is a promising clinical outcome measure that correlates well with established angiographic measurements.

Stent-assisted coiling versus coiling alone in unruptured intracranial aneurysms in the matrix and platinum science trial: safety, efficacy, and mid-term outcomes.

BACKGROUND AND PURPOSE: Stent-assisted coiling may result in less aneurysm recanalization but more complications than coiling alone. We evaluated outcomes of coiling with and without stents in the multicenter Matrix and Platinum Science Trial. MATERIALS AND METHODS: All patients in the Matrix and Platinum Science Trial with unruptured intracranial aneurysms treated per protocol were included. Baseline patient and aneurysm characteristics, procedural details, neurologic outcomes, angiographic outcomes, and safety data were analyzed. RESULTS: Overall, 137 of 361 (38%) patients were treated with a stent. Stent-coiled aneurysms had wider necks (≥4 mm in 62% with stents versus 33% without, P < .0001) and lower dome-to-neck ratios (1.3 versus 1.8, P < .0001). Periprocedural serious adverse events occurred infrequently in those treated with and without stents (6.6% versus 4.5%, P = .39). At 1 year, total significant adverse events, mortality, and worsening of mRS were similar in treatment groups, but ischemic strokes were more common in stent-coiled patients than in coiled patients (8.8% versus 2.2%, P = .005). However, multivariate analysis confirmed that at 2 years after treatment, prior cerebrovascular accident (OR, 4.7; P = .0089) and aneurysm neck width ≥4 mm (OR, 4.5; P = .02) were the only independent predictors of ischemic stroke. Stent use was not an independent predictor of ischemic stroke at 2 years (OR, 1.1; P = .94). Stent use did not predict target aneurysm recurrence at 2 years, but aneurysm dome size ≥10 mm (OR, 9.94; P < .0001) did predict target aneurysm recurrence. CONCLUSIONS: Stent-coiling had similar outcomes as coiling despite stented aneurysms having more difficult morphology than coiled aneurysms. Increased ischemic events in stent-coiled aneurysms were attributable to baseline risk factors and aneurysm morphology.

Coil embolisation of intercostal artery for operative localisation of spinal dural arterio-venous fistulae.

We describe a new method of intra-operative localisation of spinal dural arterio-venous fistulae, involving pre-operative embolisation of the appropriate intercostal artery. This method has significant advantages over other forms of spinal level localisation and has not previously been described.

Embolization of residual fistula following stereotactic radiosurgery in cerebral arteriovenous malformations.

Treatment of brain arteriovenous malformations (BAVMs) often requires a multitechnique approach. We present 2 cases of BAVM, in which initial stereotactic radiosurgery (SRS) was successful in obliterating a significant volume of the nidus. At follow-up angiography, residual fistulas were identified and selectively embolized; this procedure cured the lesions. Many series describe initial embolization to reduce the nidal volume followed by SRS to the remnant. The described cases highlight the value of primary radiosurgery followed by selective fistula embolization.

HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS trial): procedural safety and operator-assessed efficacy results.

BACKGROUND AND PURPOSE: Coated coils have been in clinical use for several years without robust evidence to determine their safety/efficacy. The HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS) addresses this deficiency for the HydroCoil embolic system. This article reports periprocedural safety/operator-assessed angiographic results from HELPS. MATERIALS AND METHODS: Patients were randomized to the hydrogel coil or control arms by using concealed allocation with minimization matching groups. Any bare platinum coils were allowed in the control arm, and assist devices could be used as clinically required. Both recently ruptured and not recently ruptured/unruptured aneurysms were included. Analysis was on an intention-to-treat basis. RESULTS: Four hundred ninety-nine patients were recruited. Coiling was successful in 98.6%. Mean aneurysm size was 6.5 mm (26% were > or =10 mm), 53% were recently ruptured aneurysms, and an assist device was used in 46%. Seventy procedural adverse events were reported in hydrogel coils and 86 in control arms. The 3-month mortality rate was 3.6% in hydrogel coils and 2.0% in control arms; the difference was not significant (P = .6). There was a lower 2-month mortality rate in the HELPS subarachnoid hemorrhage cohort (4.1%) than would be anticipated from the International Subarachnoid Aneurysm Trial (7%). There was a trend toward increased adverse events when assist devices were used, which was substantial for stents deployed in recently ruptured aneurysms. Ninety-six percent of patients discharged were World Federation of Neurosurgeons grade 0-2 at discharge. No difference was found between arms in the operator assessment of angiographic occlusions (P = .3). CONCLUSION: These HELPS results reinforce coiling as an effective treatment for aneurysms, with an excellent technical success rate. Hydrogel coils can be used in a wide spectrum of aneurysms with a risk profile equivalent to that of bare platinum.

Single-center experience of cerecyte coils in the treatment of intracranial aneurysms: initial experience and early follow-up results.

BACKGROUND AND PURPOSE: Endovascular treatment of intracranial aneurysms using platinum coils is effective, but uncommonly aneurysms recur. New-generation coils, such as Cerecyte, aim to address this problem. This study examines the safety and efficacy of these coils in the treatment of a cohort of ruptured and unruptured aneurysms MATERIALS AND METHODS: Sixty-seven patients with 68 aneurysms were included in the study. Of these, 51 were treated exclusively with the new polyglycolic acid (PGA)-containing coils, and 17 were treated with a combination of new PGA-containing and other coils. Initial and follow-up angiograms were graded according to the 3-point scale of occlusion. Follow-up angiography was available in 46 cases at 6 months. Based on occlusion grading at initial and follow-up angiography, aneurysms were classified into stable, improved, and worsened (recanalized) groups. RESULTS: Of the exclusive new-coil cohort, 36 cases (70.6%) were initially completely occluded (grade 1), 12 (23.5%) showed filling at the neck (grade 2), and 3 (5.9%) showed contrast within the neck and sac (grade 3). Analysis of the follow-up angiograms showed 24 (70.6%) had stable occlusion, 3 (8.8%) had improved occlusion, and 7 (20.6%) had worsening occlusion. Data for cases treated with new PGA-containing coils together with bare platinum coils were also analyzed separately. Intraprocedural adverse events were noted in 4 cases (7.8%), but there were no clinical sequelae. There were no rebleeds in the follow-up period. CONCLUSION: New PGA-containing coils show no excess in procedural and periprocedural complications over bare platinum coils, and the recanalization rate is comparable with bare platinum coils in the short term.

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding.

Follow-up of intracranial aneurysms treated with matrix detachable coils: a single-center experience.

BACKGROUND AND PURPOSE: Matrix coils are polymer-coated bioactive coils used in treatment of intracranial aneurysms. The current study is aimed at evaluating the efficacy and safety of these coils in treatment of ruptured and unruptured aneurysms. METHODS: Seventy-seven consecutive patients with 84 aneurysms were included in the study. Forty-six aneurysms were treated with Matrix coils alone, and 38 were treated with Matrix coils in combination with other coils/devices. Angiographic follow-up was available in 64 patients with 70 aneurysms. Length of follow-up ranged from 6 to 28 months with mean of 10 months. Both postembolization and follow-up angiograms were graded on a 3-point Raymond scale. Aneurysms were classified as stable, improved, or recanalized based on the follow-up angiograms. Recanalization was considered major if it was saccular and its size would theoretically permit retreatment with coils. RESULTS: At the end of the initial procedure, 47 (56.0%) aneurysms showed complete occlusion (Raymond 1), 20 (23.8%) showed contrast filling the neck of the aneurysm (Raymond 2), and 16 (19.0%) showed contrast filling the sac of the aneurysm (Raymond 3). Of the 70 aneurysms in which follow-up angiograms were available, 55.7% remained stable in appearance, 20.0% showed improved occlusion, and 24.3% demonstrated recanalization; 8.6% demonstrated major recanalization. There were 2 aneurysm rebleeds (both incompletely packed); one resulted in death. CONCLUSION: Matrix coils are safe to use and the recanalization rate of aneurysms treated with these coils appears to be at least comparable with historical studies with Guglielmi detachable coils.

Temporary alopecia after subarachnoid haemorrhage.

Primary endovascular intervention is increasingly the first choice of treatment for cerebral aneurysms, particularly for those with complex anatomy in the posterior circulation. However, their clinical management and follow-up continue to be predominantly in the hands of neurosurgeons. In this report, the development of alopecia following the coiling of posterior circulation aneurysms is described. The alopecia was transient and lasted for approximately 6 months, and occurred in the occipital and suboccipital regions of the scalp. This report aims to highlight this condition, which has not been previously reported in the neurosurgical literature. The potential hazards of irradiation should be borne in mind while carrying out complex endovascular procedures. The patient should be counselled and all necessary steps undertaken to limit radiation exposure.

Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord.

BACKGROUND: Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized. METHODS: The authors studied seven patients with Alexander disease, diagnosed based on mutations in the GFAP gene, who presented unusual MRI findings. The authors reviewed clinical history, MRI abnormalities, and GFAP mutations. RESULTS: All patients had juvenile disease onset with signs of brainstem or spinal cord dysfunction. None of the patients had a macrocephaly. The MRI abnormalities were dominated by medulla and spinal cord abnormalities, either signal abnormalities or atrophy. One patient had only minor cerebral white matter abnormalities. A peculiar finding was the presence of a kind of garland along the ventricular wall in four patients. Three patients had an unusual GFAP mutation, one of which was a duplication mutation of two amino acids, and one an insertion deletion. CONCLUSION: Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.

Comparison of image quality, diagnostic confidence and interobserver variability in contrast enhanced MR angiography and 2D time of flight angiography in evaluation of carotid stenosis.

The aim of this study was to compare image quality, level of diagnostic confidence and interobserver agreement in assessment of carotid stenosis with contrast enhanced MR angiography (CE MRA) in comparison with 2D time of flight MR angiography (2D TOF MRA). 60 carotid arteries in 30 patients were examined by three observers. Image quality and diagnostic confidence were assessed on the basis of a visual analogue scale. Interobserver variability was assessed with the help of intraclass correlation coefficient. Median values on the visual analogue scale for image quality and diagnostic confidence were higher for CE MRA compared with 2D TOF MRA for all three observers. Higher intraclass correlation values were recorded for interobserver variability for CE MRA compared with 2D TOF MRA both for visual estimation of carotid stenosis as well as for measurement of carotid stenosis on the basis of North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) criteria. CE MRA provides better image quality, higher level of diagnostic confidence and more interobserver agreement compared with 2D TOF MRA.

Does the method of treatment of acutely ruptured intracranial aneurysms influence the incidence and duration of cerebral vasospasm and clinical outcome?

OBJECTIVES: Cerebral vasospasm remains the leading cause of death and permanent disability after subarachnoid haemorrhage. This study determined whether the method of aneurysm treatment plays an important role in determining the incidence of cerebral vasospasm and its clinical consequences. METHODS: Admission data, cranial computed tomography (CT), treatment details, transcranial Doppler (TCD) results, and clinical outcomes of patients who had surgical or endovascular management of their ruptured aneurysm were recorded and subject to multivariate analysis. RESULTS: Between January 1995 and December 1999, 292 eligible patients (206 female, 86 male) had definitive aneurysm treatment at our unit. 212 patients were clipped, 80 coiled. There was no significant difference in patient age, pre-treatment neurological grade, Fisher grade, or timing of treatment in the two groups. 48.3% patients developed TCD detected cerebral vasospasm and 16.1% patients developed permanent ischaemic neurological deficit. At clinical follow up, 84.2% of patients were well (mGOS 1 and 2) with a cumulative death rate of 6.5% from all causes. The only significant predictor of TCD-detected cerebral vasospasm was patient age (inversely, p = 0.004). Increased patient age, vasospasm, poor pre-treatment WFNS, and higher CT Fisher grades correlated with a poor discharge GOS. However, only poor pre-treatment WFNS grade and patient age correlated with poor GOS at follow up (p<0.001). CONCLUSION: The treatment method had no influence on the incidence or duration of TCD detected vasospasm and there was no significant difference in outcome at discharge or follow up between those patients who had surgery or endovascular management of their aneurysms.

Cerebral edema associated with betaine treatment in classical homocystinuria.

A child with cystathionine beta-synthase deficiency developed cerebral edema 4 to 6 weeks after starting betaine therapy. There was no evidence of intracranial thrombosis, but there was widespread edema of the white matter. He recovered fully after emergency decompressive craniotomy and withdrawal of betaine.

Use of neuroform stent in a patient with acute stroke caused by spontaneous petrous segment internal carotid artery dissection: a case report.

SUMMARY: Neuroform stents have been recently introduced for treatment of broad-necked intracranial aneurysms. Several studies have demonstrated the feasibility of deployment of Neuroform stents (Boston Scientific Target, USA) in intracranial circulation. We report a case of a patient presenting with acute stroke due to occlusive petrous segment internal carotid artery dissection who was treated with a Neuroform stent.