Cerecyte coil trial: angiographic outcomes of a prospective randomized trial comparing endovascular coiling of cerebral aneurysms with either cerecyte or bare platinum coils.

BACKGROUND AND PURPOSE: We report the primary outcome of the Cerecyte Coil Trial, a randomized trial to determine whether polymer-loaded Cerecyte coils compared with Micrus bare platinum coils improved the proportion of patients with angiographic occlusion of the aneurysm at 6 months when assessed by a core laboratory. The secondary objectives were to compare the clinical outcomes and retreatment rates in the 2 groups. METHODS: Five hundred patients between 18 and 70 years of age with a ruptured or unruptured target aneurysm were randomized to be treated with either Cerecyte or bare platinum coils in 23 centers worldwide. Two hundred forty-nine patients were assigned to Cerecyte coils and 251 to bare platinum coils. Analysis was by intention to treat. RESULTS: Four hundred ninety-four patients were eligible for analysis. Four hundred eighty-one patients underwent coil treatment of their aneurysm, 227 patients with recently ruptured aneurysms and 254 with unruptured aneurysms. Four hundred thirty-three follow-up angiograms were assessed by the core laboratory; 127 of 215 (59%) and 118 of 218 (54%) in the Cerecyte and bare platinum groups, respectively, fulfilled the trial prespecified definition of success, namely that the treated aneurysm showed complete angiographic occlusion, had stable neck remnant, or improved in angiographic appearance compared with the end-of-treatment angiogram (P=0.17). Late retreatment was performed in 25 of 452 (5.5%) patients, 17 (7.7%) Cerecyte versus 8 (3.5%) bare platinum (P=0.064; range, 4-34 months). The clinical outcomes did not differ between the groups. CONCLUSIONS: There was no significant difference at 6 months in the angiographic outcomes between Cerecyte coils and bare platinum coils when assessed by the core laboratory. Clinical Trial Registration Information- URL: www.controlled-trials.com. Unique Identifier: ISRCTN82461286.

A historical analysis of single-stage γ knife radiosurgical treatment for large arteriovenous malformations: evolution and outcomes.

BACKGROUND: Large arteriovenous malformations (AVMs) remain challenging and difficult to treat, reflected by evolving strategies developed from simple radiosurgical plans, to encompass embolization and, recently, staged volume treatments. To establish a baseline for future practice, we reviewed our clinical experience. METHOD: The outcomes for 492 patients (564 treatments) with AVMs >10 cm(3) treated by single-stage radiosurgery were retrospectively analysed in terms of planning, previous embolization and size. RESULTS: Twenty-eight percent of the patients presented with haemorrhage at a median age of 29 years (range: 2-75). From 1986 to 1993 (157 patients) plans were simplistic, based on angiography using a median of 2 isocentres and a marginal dose of 23 Gy covering 45-70% of the AVM (median volume 15.7 cm(3)). From 1994 to 2000 (225 patients) plans became more sophisticated, a median of 5 isocentres was used, covering 64-95% of the AVM (14.6 cm(3)), with a marginal dose of 21 Gy. Since 2000, MRI has been used with angiography to plan for 182 patients. Median isocentres increased to 7 with similar coverage (62-94%) of the AVM (14.3 cm(3)) and marginal dose of 21 Gy. Twenty-seven percent, 30% and 52% of patients achieved obliteration at 4 years, respectively. The proportion of prior embolization increased from 9% to 44% during the study. Excluding the embolized patients, improvement in planning increased obliteration rates from 28% to 36% and finally 63%. Improving treatment plans did not significantly decrease the rate of persisting radiation-induced side effects (12-16.5%). Complication rate rose with increasing size. One hundred and twenty-three patients underwent a second radiosurgical treatment, with a 64% obliteration rate, and mild and rare complications (6%). CONCLUSIONS: Better visualization of the nidus with multimodality imaging improved obliteration rates without changing morbidity. Our results support the view that prior embolization can make interpretation of the nidus more difficult, reducing obliteration rate. It will be important to see how results of staged volume radiosurgery compare with this historical material.

Mechanical thrombectomy for acute stroke in pregnancy.

Several recent randomised control trials have shown adjunctive endovascular mechanical thrombectomy to be an effective and safe treatment for acute stroke superior to medical therapy alone. Despite this, questions remain over certain groups of patients that have been excluded from these studies, such as pregnant women. We believe this is a topic of increasing clinical significance with minimal data in the literature. In this article we discuss stroke in pregnancy and highlight the important technical considerations of endovascular mechanical thrombectomy, including minimising radiation exposure to the mother and fetus.

Persistent hypoglossal artery aneurysm: Case report and qualitative systematic review.

A persistent hypoglossal artery was first described in 1889 and is one of the more common anatomical variations arising from aberration in normal development. Endovascular coiling has been recognised as a robust treatment for acutely ruptured intracranial arterial aneurysms, although specific data regarding an aneurysm arising from a persistent hypoglossal artery is lacking due to the low incidence. Here we report both the oldest patient reported to be treated with a persistent hypoglossal artery-associated aneurysm and also explicitly report endovascular treatment of a persistent hypoglossal artery aneurysm arising at the posterior inferior cerebellar artery origin. Qualitative systematic review of the available medical literature demonstrates limited evidence regarding treatment of persistent hypoglossal artery-associated aneurysms with the majority being carried out via open surgery. Ruptured posterior inferior cerebellar artery aneurysm arising from a persistent hypoglossal artery can be successfully and safely treated by endovascular therapy via the persistent hypoglossal artery. Randomised study of this situation is unlikely to be feasible; however, qualitative review of the literature reveals six such aneurysms that have been treated surgically, and this case appears to be the first via an endovascular means.

Management of Concomitant Moyamoya Disease, Arterial Venous Malformation, and Intracranial Aneurysm: Case Illustration, Literature Review, and Management Algorithm.

BACKGROUND: Moyamoya disease (MMD), arterial venous malformations (AVMs), and intracranial aneurysms are distinct cerebrovascular disease processes that most commonly occur in isolation. The literature on the treatment algorithm of each individual condition is well established. An association between MMD and intracranial aneurysms is also known, but MMD in association with AVM is rare. CASE DESCRIPTIONS: The authors discuss various dilemmas in the multimodality management of these conditions when they coexist with an illustrative case of a 46-year-old woman who presented following a stroke, with 1) left-sided MMD, 2) left-sided frontal AVM, and 3) an aneurysm arising from the A1 segment of the right anterior cerebral artery. These were managed respectively by 1) the left external carotid artery to M2 segment of middle cerebral artery bypass using an autologous radial artery graft and left indirect superior temporal artery-encephaloduroarteriosynangiosis, 2) stereotactic radiosurgery, and 3) endovascular coiling of the aneurysm. Three years following intervention, cerebral angiography showed a patent bypass, complete obliteration of the AVM, and no residual filling of the coiled aneurysm. CONCLUSIONS: Our strategy of surgical revascularization for MMD, radiosurgery for AVM, and endovascular coiling for aneurysm resulted in a positive long-term clinical outcome. In view of the rarity of the condition, the authors propose a management algorithm for such patients.

Cervical cord decompression following embolisation of a giant cervical vertebro-vertebral arteriovenous fistula.

Arteriovenous fistulation between the vertebral arteries to extradural (epidural) veins, termed vertebro-vertebral arteriovenous fistulae, are uncommon diagnoses without established diagnostic algorithms or treatment options. Minimal evidence exists describing the management of this pathology. Endovascular treatment was performed under general anaesthesia by coil occlusion of the vertebral artery from the point of the fistula to the mid-vertebral artery. Repeat magnetic resonance angiographic imaging one week following the procedure confirmed an 80% reduction in the size of the epidural vein and decompression of the cervical spinal cord. At four-week follow-up there was significant qualitative improvement in the myelopathic symptoms including walking distance and pain. Normal physiological filling of the collapsed extradural vein was observed on follow-up digital subtraction angiography at five months. Catheter angiography by an experienced interventional neuro-radiologist is critical in defining the anatomy and providing minimally invasive treatment.

Staged-Volume Radiosurgery of Large Arteriovenous Malformations Improves Outcome by Reducing the Rate of Adverse Radiation Effects.

Background: The treatment of large arteriovenous malformations (AVMs) remains challenging. Recently, staged-volume radiosurgery (SVRS) has become an option. Objective: To compare the outcome of SVRS on large AVMs with our historical, single-stage radiosurgery (SSRS) series. Methods: We have been prospectively collecting data of patients treated by SVRS since 2007. There were 84 patients who had a median age of 37 years (range, 9-62 years) who were treated until July 2013. The outcomes of 76 of those who had follow-ups available were analyzed and compared with the outcomes of 122 patients treated with the best SSRS technique. Results: There were 21.5% of AVMs that were deep seated, and 44% presented with hemorrhage resulting in 45% fixed neurological deficit. There were 14% of patients who had undergone embolization before radiosurgery. The median nidus treatment volume was 19.7 cm3 (6.65-68.7) and 17.5 Gy (13-22.5) prescription isodose was given. Of the 44 lesions having radiological follow-up at 4 years, 61.4% were completely obliterated. Previous embolization (50% with and 63% without) and higher Spetzler-Martin grades appeared to be the negative factors in successful obliteration, but treatment volume was not. Within 3 years after radiosurgery, the annual bleed rates of unruptured and previously ruptured AVMs were 3.2% and 5.6%, respectively. Three bleeds were fatal and 2 resulted in significant modified Rankin scale 3 morbidity. These rates differ little from SSRS. Temporary adverse radiation effects (AREs) did not change significantly, but permanent AREs dropped from 15% to 6.5% (P = .03) compared with SSRS. Conclusion: Obliteration and hemorrhage rates of large AVMs treated by SVRS are similar to historical SSRS. However, SVRS offers a lower rate of AREs.

Modeling of the acute effects of primary hypertension and hypotension on the hemodynamics of intracranial aneurysms.

Hemodynamics is a risk factor in intracranial aneurysms (IA). Hypertension and pharmacologically induced hypotension are common in IA patients. This study investigates how hypertension and hypotension may influence aneurysmal hemodynamics. Images of 23 IAs at typical locations were used to build patient-specific Computational Fluid Dynamics models. The effects of hypotension and hypertension were simulated through boundary conditions by modulating the normotensive flow and pressure waveforms, in turn produced by a 1D systemic vascular model. Aneurysm location and flow pattern types were used to categorize the influence of hypotension and hypertension on relevant flow variables (velocity, pressure and wall shear stress). Results indicate that, compared to other locations, vertebrobasilar aneurysms (VBA) are more sensitive to flow changes. In VBAs, space-averaged velocity at peak systole increased by 30% in hypertension (16-21% in other locations). Flow in VBAs in hypotension decreased by 20% (10-13% in other locations). Momentum-driven hemodynamic types were also more affected by hypotension and hypertension, than shear-driven types. This study shows how patient-specific modeling can be effectively used to identify location-specific flow patterns in a clinically-relevant study, thus reinforcing the role played by modeling technologies in furthering our understanding of cardiovascular disease, and their potential in future healthcare.

Pediatric head and neck lesions: assessment of vascularity by MR digital subtraction angiography.

BACKGROUND AND PURPOSE: Pediatric head and neck lesions can be difficult to characterize on clinical grounds alone. We investigated the use of dynamic MR digital subtraction angiography as a noninvasive adjunct for the assessment of the vascularity of these abnormalities. METHODS: Twelve patients (age range, 2 days to 16 years) with known or suspected vascular abnormalities were studied. Routine MR imaging, time-of-flight MR angiography, and MR digital subtraction angiography were performed in all patients. The dynamic sequence was acquired in two planes at one frame per second by using a thick section (6-10 cm) selective radio-frequency spoiled fast gradient-echo sequence and an IV administered bolus of contrast material. The images were subtracted from a preliminary mask sequence and viewed as a video-inverted cine loop. RESULTS: In all cases, MR digital subtraction angiography was successfully performed. The technique showed the following: 1) slow flow lesions (two choroidal angiomas, eyelid hemangioma, and scalp venous malformation); 2) high flow lesions that were not always suspected by clinical examination alone (parotid hemangioma, scalp, occipital, and eyelid arteriovenous malformations plus a palatal teratoma); 3) a hypovascular tumor for which a biopsy could be safely performed (Burkitt lymphoma); and 4) a hypervascular tumor of the palate (cystic teratoma). CONCLUSION: Our early experience suggests that MR digital subtraction angiography can be reliably performed in children of all ages without complication. The technique provided a noninvasive assessment of the vascularity of each lesion that could not always have been predicted on the basis of clinical examination or routine MR imaging alone.

Contrast-enhanced fluid-attenuated inversion recovery imaging for leptomeningeal disease in children.

BACKGROUND AND PURPOSE: To develop an MR imaging method that improves detection of leptomeningeal disease when compared with the current reference standard, contrast-enhanced T1-weighted imaging. METHODS: We investigated the cases of 10 children who were at high risk of intracranial leptomeningeal disease (Sturge-Weber syndrome and medulloblastoma). The cases of Sturge-Weber syndrome were investigated by using one MR imaging examination, and the cases of medulloblastoma were investigated by using four MR imaging examinations performed over 18 months. In all cases, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images were acquired in addition to the routine sequences. The parameters of the FLAIR sequence were chosen to maximize the T1 component of the signal intensity, to maximize detection of leptomeningeal enhancement. We made subjective and objective assessments of the presence and extent of leptomeningeal disease as shown on contrast-enhanced T1-weighted images and contrast-enhanced FLAIR images. RESULTS: In three of the four cases of Sturge-Weber syndrome, the T1 and FLAIR sequences showed comparable extent of leptomeningeal enhancement. For one child, FLAIR images showed unexpected bilateral disease and more extensive leptomeningeal enhancement on the clinically suspected side. In four of six cases of medulloblastoma, no leptomeningeal enhancement was shown on any examinations during the 18-month period. In two cases, FLAIR images showed more extensive leptomeningeal enhancement when compared with T1-weighted images. CONCLUSION: Contrast-enhanced FLAIR imaging seems to improve detection of leptomeningeal disease when compared with routine contrast-enhanced T1-weighted imaging. This seems to be partly because of suppression of signal intensity from normal vascular structures on the surface of the brain by FLAIR, which allows easier visualization of abnormal leptomeninges. We think that these findings can be extrapolated to the investigation of leptomeningeal disease of all causes and at all ages.

Endovascular trapping of traumatic carotid-cavernous fistulae.

We describe an unconventional endovascular approach to the treatment of traumatic carotid-cavernous fistulas. Four patients with large high-flow shunts have been successfully treated by trapping of the fistula by using a combination of proximal balloon occlusion and distal coil embolization. The latter was achieved following retrograde catheterization of the distal parent vessel via the contralateral carotid or ipsilateral vertebral artery.

Dural arteriovenous fistulae: noninvasive diagnosis with dynamic MR digital subtraction angiography.

MR digital subtraction angiography (DSA) is a new diagnostic tool capable of producing dynamic images of the cerebral circulation with the injection of gadopentetate dimeglumine into a peripheral vein. Previous reports have concentrated on its potential as a noninvasive technique for the study of pial arteriovenous malformations. In this report, we present our early findings with MR DSA in the evaluation of intracranial dural arteriovenous fistulae.

Intracranial dural arteriovenous malformations: results of stereotactic radiosurgery in 17 patients.

AIM: To assess the efficacy of stereotactic radiosurgery (STRS) for the treatment of dural arteriovenous fistulae (DAVF). MATERIALS AND METHODS: Between November 1987 and December 1998, 17 patients with a total of 18 DAVF were treated with STRS at the National Centre for Stereotactic Radiosurgery, Sheffield. Clinical and radiological data was collected retrospectively from the case notes and radiological records. Two neuroradiologists classified the pre-STRS appearance of the DAVF using the Borden criteria, and reviewed the follow-up imaging. Up to date follow-up was requested from the GPs and referring consultants. RESULTS: In retrospect one DAVF had been misdiagnosed and was excluded from the study. The remaining 17 DAVF were located at the tentorium (6), cavernous sinus (3), right parasellar region (1), floor of left middle cranial fossa (1), midline posterior fossa (1), petrous apex (1) and transverse sinus (4). Ten were Borden type I, four were type II, three were type III. Follow-up angiography was available for 13 patients; 10 DAVF were completely obliterated, two showed considerable reduction in size, one showed deterioration. Clinical follow-up was available for 14 of the 16 patients. CONCLUSION: Stereotactic radiosurgery can successfully obliterate DAVF with few side effects.

Intracranial hypertension in Sturge-Weber/Klippel-Trenaunay-Weber overlap syndrome due to impairment of cerebral venous outflow.

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare mesodermal phakomatosis characterized by (1) cutaneous haemangiomata (usually unilateral and involving an extremity) (2) venous varicosities and (3) osseous and soft tissue hypertrophy, also of the affected limb. Sturge-Weber Syndrome (SWS), also a mesodermal phakamatosis, is characterized by meningofacial angiomatosis with cerebral calcification. Overlap between KTWS and SWS is recognized. We describe the case of a young woman with features of both KTWS and SWS who presented with symptoms of acute intracranial hypertension, including headache, vomiting and marked visual impairment. Cerebral angiography revealed paucity of the superficial cortical veins overlying one of the cerebral hemispheres and centripetal venous drainage via small deep venous channels. Based upon this pattern of cerebral venous outflow, we postulate a mechanism to explain the acute episode of intracranial hypertension.

Bispectral index detects intraoperative cerebral ischaemia during balloon assisted cerebral aneurysm coiling.

Bispectral index (BIS) is a monitoring modality designed and used for monitoring depth of anaesthesia. We wish to report a case where BIS monitoring may have alerted us to a potential adverse neurological event during angiographic coiling of a cerebral aneurysm.

Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions.

BACKGROUND: Radiosurgery is widely used to treat deep eloquent arteriovenous malformations (AVMs). OBJECTIVE: To evaluate how anatomic location, AVM size, and treatment parameters define outcome. METHODS: Retrospective analysis of 356 thalamic/basal ganglia and 160 brainstem AVMs treated with gamma knife radiosurgery. RESULTS: Median volume was 2 cm (range, 0.02-50) for supratentorial and 0.5 cm (range, 0.01-40) for brainstem AVMs; the marginal treatment doses were 17.5 to 25 Gy. After single treatment, obliteration was achieved in 65% of the brainstem, in 69% of the supratentorial, and 40% of the peritectal AVMs. Obliteration of lesions <4 cm was better in the brainstem (70%) and in the supratentorium (80%), but not in the peritectal region (40%). Complications were rare (6%-15%) and mild (≤ modified Rankin scale [MRS] 2). Rebleed rate increased with size, but was not higher than before treatment. AVMs >4 cm in the brainstem were treated with unacceptable morbidity and low cure rate. Obliteration of large supratentorial AVMs was 65% to 47% with more complications ≥ MRS3. Repeat radiosurgical treatment led to obliteration in 66% of the cases with minor morbidity. CONCLUSION: Deep eloquent AVMs <4 cm can be treated safely and effectively with radiosurgery. Obliteration of peritectal AVMs is significantly lower after a single treatment. However, morbidity is low, and repeat treatment leads to good obliteration. Radiosurgical treatment >4 cm in the brainstem is not recommended. Supratentorial deep AVMs >8 cm can be treated with radiosurgery with higher risk and lower obliteration rate. However, these lesions are difficult to treat with other treatment modalities, and a 50% success rate makes radiosurgery a good alternative even in this challenging group.

Multiple sclerosis in an adrenoleukodystrophy carrier.

X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder, in which accumulation of very long chain fatty acids (VLCFAs) results in damage to the central nervous system. As the disease is X-linked, males are affected severely, but female carriers may also present with neurological symptoms. We report the case of a young adult female, who presented with episodic sensorimotor symptoms. Although she was a heterozygous female carrier of X-ALD, subsequent investigations confirmed a diagnosis of multiple sclerosis (MS). To the best of our knowledge, this is the first reported case of a female X-ALD carrier in which the clinical features were more consistent with co-existent MS than ALD-related pathology. The case serves as a reminder that alternative, more common diagnoses should also be considered in carriers of rare neurological syndromes.

Computational hemodynamics in cerebral aneurysms: the effects of modeled versus measured boundary conditions.

Modeling of flow in intracranial aneurysms (IAs) requires flow information at the model boundaries. In absence of patient-specific measurements, typical or modeled boundary conditions (BCs) are often used. This study investigates the effects of modeled versus patient-specific BCs on modeled hemodynamics within IAs. Computational fluid dynamics (CFD) models of five IAs were reconstructed from three-dimensional rotational angiography (3DRA). BCs were applied using in turn patient-specific phase-contrast-MR (pc-MR) measurements, a 1D-circulation model, and a physiologically coherent method based on local WSS at inlets. The Navier-Stokes equations were solved using the Ansys®-CFX™ software. Wall shear stress (WSS), oscillatory shear index (OSI), and other hemodynamic indices were computed. Differences in the values obtained with the three methods were analyzed using boxplot diagrams. Qualitative similarities were observed in the flow fields obtained with the three approaches. The quantitative comparison showed smaller discrepancies between pc-MR and 1D-model data, than those observed between pc-MR and WSS-scaled data. Discrepancies were reduced when indices were normalized to mean hemodynamic aneurysmal data. The strong similarities observed for the three BCs models suggest that vessel and aneurysm geometry have the strongest influence on aneurysmal hemodynamics. In absence of patient-specific BCs, a distributed circulation model may represent the best option when CFD is used for large cohort studies.

Stereotactic radiosurgery for deep-seated cavernous malformations: a move toward more active, early intervention. Clinical article.

OBJECT: The role of radiosurgery in the treatment of cavernous malformations (CMs) remains controversial. It is frequently recommended only for inoperable lesions that have bled at least twice. Rehemorrhage can carry a substantial risk of morbidity, however. The authors reviewed their practice of treating deep-seated inoperable CMs to assess the complication rate of radiosurgery, the impact that radiosurgery might have on rebleeding, and whether a more active, earlier intervention is justified in managing this condition. METHODS: The authors performed a retrospective analysis of 113 patients with 79 brainstem and 39 thalamic/basal ganglia CMs treated with Gamma Knife surgery. Lesions were stratified into 2 groups: those that might be lower risk with no more than 1 symptomatic bleed before radiosurgical treatment and those deemed high risk with multiple symptomatic hemorrhages before treatment. RESULTS: Forty-one CMs had multiple symptomatic hemorrhages before radiosurgery with a first-ever bleed rate of 2.9% per lesion per year, a rebleed rate of 30.5% per lesion per year, and a median time of 1.5 years between the first and second bleeds. In this group the rebleed rate decreased to 15% for the first 2 years after radiosurgery and declined further to 2.4% thereafter. Pretreatment multiple bleeds led to persistent deficits in 72% of the patients. Seventy-seven CMs had no more than 1 symptomatic bleed before radiosurgery, making for a lifetime bleed rate of 2.2% per lesion per year. The short period between the presenting bleed and treatment (median 1 year) makes the natural history in this group uncertain. The rate of hemorrhage in the first 2 years after treatment was 5.1%, and 1.3% thereafter. Pretreatment hemorrhages resulted in permanent deficits in 43% of the patients in this group, a rate significantly lower than in the multiple-bleeds group (p < 0.001). Posttreatment hemorrhages led to persistent deficits in only 7.3% of the patients. Permanent adverse radiation effects were rare (7.3%) and minor in both groups. CONCLUSIONS: Stereotactic radiosurgery is a safe management strategy for CMs in eloquent sites with the marked advantage of reducing rebleed risks in patients with repeated pretreatment hemorrhages. The benefit in treating CMs with a single bleed is less clear. Note, however, that repeated hemorrhage carries a significant risk of increased morbidity far in excess of any radiosurgery-related morbidity, and the authors assert that this finding justifies the early active management of deep-seated CMs.