The ARUBA trial: current status, future hopes.

BACKGROUND AND PURPOSE: Report on the status of an on-going National Institutes of Neurological Disorders and Stroke (NINDS)-supported clinical trial of management of unbled brain arteriovenous malformations. SUMMARY OF REVIEW: Begun in April 2007 with 3 centers, the trial has grown to 65 centers, and has randomized 124 patients through mid-June 2010 en route to the planned 400. The current literature continues to support the rationale for the trial. CONCLUSIONS: ARUBA is steadily approaching its monthly randomization goals and has already reached the number needed to test the maximum published interventional complication rates against the minimum hemorrhage rates for natural history.

De novo formation of large arteriovenous shunting and a vascular nidus mimicking an arteriovenous malformation within an anaplastic oligodendroglioma: treatment with embolization and resection.

The authors report the de novo occurrence and treatment of an arteriovenous lesion within an anaplastic oligodendroglioma in a patient with previously unremarkable brain imaging. Intracranial arteriovenous malformations (AVMs) are believed to be congenitally acquired lesions, and their association with brain neoplasms is extremely rare. Diagnostic imaging revealed a mass lesion with large arteriovenous shunts and a vascular nidus mimicking a true AVM. Histological and immunohistochemical testing showed an anaplastic oligodendroglioma mixed with an AVM. The clinical, radiological, and operative data are reviewed, as are the histopathological findings. To the authors' knowledge this is the first case of de novo occurrence of an arteriovenous lesion with large shunts and a vascular nidus within an anaplastic oligodendroglioma.

Wingspan stenting of symptomatic extracranial vertebral artery stenosis and perioperative evaluation using quantitative magnetic resonance angiography: report of two cases.

The best management strategy for symptomatic vertebrobasilar ischemia is currently not well-defined. Noninvasive Optimal Vessel Analysis (NOVA, VasSol, Inc.) is computer software that, using quantitative magnetic resonance (MR) angiography technology, represents the only commercially available means of noninvasively measuring blood flow within the human vasculature. The author used quantitative MR angiography to study cerebral blood flow in 2 patients who underwent angioplasty and stenting for medically refractory extracranial cervical vertebral artery (VA) stenosis using the recently Food and Drug Administration-approved WingSpan stent (Boston Scientific, Target). WingSpan stents were successfully placed after balloon angioplasty in both patients without complications. At the 5-month clinical follow-up examination, 1 patient was symptom free and the other had had a possible transient ischemic attack without sequelae. The WingSpan stent may represent an alternative management scheme for symptomatic vertebrobasilar ischemia from extracranial VA stenosis. Quantitative MR angiography can readily measure blood flow in the vertebrobasilar system, and these values correlated with the angiographic outcomes in the 2 patients treated in the present study.

Endovascular treatment of acute ischaemic stroke.

The emphasis of treatments for acute ischaemic stroke during the past two decades has been on revascularisation. Endovascular treatment is a promising alternative for patients who are ineligible for standard intravenous thrombolytic therapy; however, its use is limited by the few randomised trials reported and the small number of practising neurointerventionalists. Although data are still being collected, important progress has been made. In this Review, we summarise the findings of the major clinical trials of endovascular treatment, and show that endovascular treatment of acute ischaemic stroke is a therapeutic option for patients who are disqualified from or do not improve on treatment with intravenous alteplase. Moreover, the American Heart Association has expanded its guidelines to include endovascular stroke therapies as a treatment option.

Transarterial embolization of vein of Galen malformations: the use of magnetic resonance imaging noninvasive optimal vessel analysis to quantify shunt reduction. Report of two cases.

In patients with vein of Galen malformations, high-flow shunting decreases cerebral perfusion. By reducing or eliminating these shunts, transarterial embolization can improve cerebral perfusion and clinical outcomes. Quantifying pre- and postembolization shunt blood flow may help determine the optimal timing and efficacy of embolization and may provide prognostic information. The authors used magnetic resonance imaging noninvasive optimal vessel analysis as a novel modality to measure volumetric blood flow through vein of Galen malformation shunts in a neonate and an infant before and after transarterial embolization.

Neurointerventional treatment of vasospasm.

OBJECTIVES: To review the historical development and current status of endovascular techniques used in the treatment of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage. METHODS: This article summarizes the relevant literature on neurointerventional therapy for vasospasm, namely instillation of intraarterial medication (papaverine, nicardipine, verapamil) and transluminal balloon angioplasty. The authors synthesize the available literature with their own experience using the various endovascular modalities to treat vasospasm at high volume cerebrovascular centers. TECHNIQUE: Indications for the use of neurointerventional therapy as well as a summary of the technique for transluminal angioplasty to treat vasospasm as employed by the authors is described. DISCUSSION: Neurointerventional treatment of vasospasm following aneurysmal hemorrhage has been proven to be a safe and successful technique for those patients suffering symptomatic vasospasm refractory to medical management. The techniques contunue to undergo refinement as endovascular technology advances. We currently favor the use of balloon angioplasty over intraarterial antispasmotics due to the increased durability and long-lasting effects of the former and lower risk profile.

Successful emergent angioplasty of neurosarcoid vasculitis presenting with strokes.

BACKGROUND: Sarcoidosis is a systemic disease with neurologic involvement in approximately 5% of cases. Ischemic events related to neurosarcoid vasculitis are rare. We report the successful treatment of symptomatic neurosarcoid vasculitis with angioplasty. CASE DESCRIPTION: A 41-year-old African American with a diagnosis of neurosarcoid presented with aphasia and right-sided weakness. He was treated medically with antiplatelet agents, heparinization, and hypertensive therapy. Despite this treatment, he experienced clinical worsening and radiographic extension of his infarcts. He underwent successful angioplasty of a severe focal stenosis of the left middle cerebral artery. After the procedure, he experienced marked improvement in his symptoms and at follow-up continues to improve. CONCLUSIONS: We report the angiographic demonstration of neurosarcoidosis with large vessel changes and resultant strokes and its successful treatment with balloon angioplasty.

Treatment options for wide-necked intracranial aneurysms using a self-expandable hydrophilic coil and a self-expandable stent combination.

The endovascular treatment of wide-necked intracranial aneurysms is evolving. We report our initial experience in treating seven wide-neck intracranial aneurysms by using a new self-expanding stent, the Neuroform, in combination with a new generation of coils that incorporate a self-expandable hydrophilic lining, the HydroCoil.

Multiple cerebral aneurysms in a neonate: occlusion and rupture.

Aneurysmal subarachnoid hemorrhage in a neonate is exceedingly uncommon. The authors report the case of a neonate with a large anterior communicating artery aneurysm, accessory left middle cerebral artery aneurysm, and left internal carotid artery (ICA) fusiform aneurysm. The neonate suffered from occlusion of the left ICA and aneurysm rupture. The large aneurysm was treated with detachable coils and the patient made a significant recovery. Of the 15 case reports of cerebral aneurysms in neonates that have been published, none has contained a description of multiple aneurysms or a discussion of endovascular treatment.

Pediatric nonvertebral paraspinal arteriovenous fistulas along the segmental nerve: clinical, imaging, and therapeutic considerations.

OBJECT: The authors characterize the clinical presentation and imaging features of paraspinal nonvertebral arteriovenous fistulas (AVFs) along the segmental nerve and describe their endovascular treatment. METHODS: The authors undertook a retrospective review of medical records, imaging, and treatment of patients with endovascular problems spanning the period from 1985 to 2003. Five pediatric patients (2-3 years of age) received diagnoses of nonvertebral paraspinal AVFs along the segmental nerve. All patients presented with an incidentally discovered continuous murmur over the paraspinal or parasternal regions. All patients were neurologically intact; two patients had cardiomegaly. The AVF was found in the midthoracic level in four patients and at L-3 in one patient. All AVFs were high-flow single-hole fistulas at the neural foramen with venous drainage into paraspinal and epidural veins but without intradural reflux. All fistulas were endovascularly occluded in the same session as diagnostic angiography took place. The fistula was completely occluded, with detachable coils in one case and with N-butyl-cyanoacrylate (NBCA) in four cases. Before NBCA injection, the flow through the fistula was decreased either by placing coils distal to the fistula or by inflating a balloon proximally. No signs of recanalization appeared on short-term follow-up magnetic resonance imaging in all patients. All patients remained neurologically intact at the last available follow-up session (mean 6 years). CONCLUSIONS: Nonvertebral paraspinal AVFs along the segmental nerve are specific disease entities seen in children presenting with bruit and cardiomegaly. Endovascular embolization should be the treatment of choice for this rare disease.

Phosphorylation of P42/P44 MAP kinase and DNA fragmentation in the rat perforant pathway stimulation model of limbic epilepsy.

The intracellular signaling pathways associated with neuronal injury after perforant pathway stimulation of the rodent hippocampus have not been examined. To determine whether activation of the p42/p44 (Erk1/2) MAP kinase (MAPK) phosphorylation cascade is linked to neuronal injury after perforant pathway stimulation (PPS), we stained for phosphorylated Erk1/2 (P-Erk1/2) and for DNA fragmentation, a marker of cell death after PPS. Eighteen Sprague-Dawley rats underwent PPS for 6 (n=6), 12 (n=6), or 24 (n=6) h and were sacrificed either immediately (n=9) or 48 h (n=9) after stimulation. Sham-operated non-stimulated control animals (n=2) and control animals receiving low frequency stimulation only (n=4) were also examined. Brain sections were stained for DNA fragmentation and P-Erk1/2. DNA fragmentation was evident only in granule cells and CA3 pyramidal cells of the stimulated side 48 h after 24 h of PPS. PPS resulted in robust phosphorylation of Erk1/2 that displayed a stereotyped timecourse, appearing first in hilar neurons on the ipsilateral side and later in hilar neurons, granule cells, hippocampal pyramidal and non-neuronal cell populations on both the stimulated and contralateral sides. Both Erk1/2 phosphorylation and DNA fragmentation show definite and reproducible staining patterns after PPS that vary based on duration of stimulation. Populations displaying Erk1/2 activation appeared to differ from those showing DNA fragmentation and neuronal injury.

Simultaneous bilateral internal carotid artery 3D rotational angiography.

We simultaneously injected both internal carotid arteries (ICAs) during 3D rotational digital subtraction angiography in a patient with a ruptured anterior communicating artery (Acom) aneurysm and vasospasm. Shaded surface display (SSD) images from this acquisition provided more anatomic detail than did SSD images created from individual ICA 3D rotational digital subtraction angriography. In the evaluation of complex Acom aneurysms, this technique can facilitate the choice of optimal working projections for safer aneurysm coiling.

Thrombus formation during intracranial aneurysm coil placement: treatment with intra-arterial abciximab.

BACKGROUND AND PURPOSE: The management of thrombus formation during coil placement in an intracranial aneurysm is important in minimizing periprocedural morbidity and mortality. We report on seven cases in which the primary treatment for thrombus formation during such coil placement was intra-arterial abciximab infusion. METHODS: Clinical and radiologic records of 100 consecutive patients who underwent coil placement in intracranial aneurysms at our institution during a 1-year period were reviewed. We identified seven cases (four ruptured aneurysms, three unruptured aneurysms) in which thrombus formation occurred during the procedure. RESULTS: Intra-arterial abciximab infusion, up to 5 mg, completely dissolved the thrombus in four of seven patients and almost completely dissolved it in two. In one patient with distal emboli, recanalization was not achieved. In two patients, an intravenous bolus of abciximab without 12-hour infusion was also given adjunctively. In one patient, leakage of contrast material occurred; this was related to the intra-arterial infusion. Clinically, no new neurologic deficits were directly related to the intra-arterial abciximab infusion. Six patients had good clinical outcome, and one patient died. CONCLUSION: Relatively low-dose, intra-arterial abciximab infusion can immediately dissolve an acute thrombus that forms during intracranial aneurysm coil placement. Although neither the optimal dose of intra-arterial abciximab nor the need to supplement the intra-arterial infusion with intravenous administration was established, we preliminarily found that low-dose intra-arterial abciximab infusion may be relatively effective and safe in this setting, even in patients with acute subarachnoid hemorrhage.

Radiosurgery of the rat hippocampus: magnetic resonance imaging, neurophysiological, histological, and behavioral studies.

OBJECTIVE: To explore the histological, electrophysiological, radiological, and behavioral effects of radiosurgery using a new model of proton beam radiosurgery (PBR) of the rodent hippocampus. METHODS: Forty-one rats underwent PBR of the right hippocampus with nominal doses of 5 to 130 cobalt Gray equivalents (CGE). Three control animals were untreated. Three months after PBR, 41 animals were evaluated with the Morris water maze, 23 with T2-weighted magnetic resonance imaging, and 22 with intrahippocampal microelectrode recordings. Animals that were studied physiologically were killed, and their brains were examined with Nissl staining and immunocytochemical staining for glutamic acid decarboxylase, heat shock protein 72 (HSP-72), parvalbumin, calmodulin, calretinin, calbindin, and somatostatin. RESULTS: Ninety and 130 CGE resulted in decreased performance in the Morris water maze, increased signal on T2-weighted magnetic resonance imaging, diminished granule cell field potentials, and tissue necrosis, which was restricted to the irradiated side. These doses also resulted in ipsilateral up-regulation of calbindin and HSP-72. Parvalbumin was down-regulated at 130 CGE. The 30 and 60 CGE animals displayed a marked increase in HSP-72 staining on the irradiated side but no demonstrable cell loss. No asymmetries were noted in somatostatin, calretinin, and glutamic acid decarboxylase staining. Normal physiology was found in rats receiving up to 60 CGE. CONCLUSION: This study expands our understanding of the effects of radiosurgery on the mammalian brain. Three months after PBR, the irradiated rat hippocampus demonstrates necrosis at 90 CGE, but not at 60 CGE, with associated abnormalities in magnetic resonance imaging, physiology, and memory testing. HSP-72 was up-regulated at nonnecrotic doses.

Intentional partial coil occlusion followed by delayed clip application to wide-necked middle cerebral artery aneurysms in patients presenting with severe vasospasm. Report of two cases.

The treatment of ruptured cerebral aneurysms in patients presenting with vasospasm remains a particular challenge. The authors treated two patients harboring Hunt and Hess Grade 1 subarachnoid hemorrhages from middle cerebral artery (MCA) aneurysms associated with severe local angiographically demonstrated yet asymptomatic vasospasm on presentation. Because both aneurysms had wide necks and were located at the MCA bifurcation, they were believed to be anatomically suitable for microsurgical clip application. Severe M, vasospasm was believed to be a relative contraindication to open surgery, however. An intentionally staged endovascular and microsurgical treatment strategy was planned in each patient. Partial coil occlusion of the aneurysmal dome was performed to prevent the lesion from rebleeding and was followed by balloon angioplasty of the spastic vessel. Early treatment of the severe spasm appeared to prevent significant delayed neurological ischemic deficit. Following resolution of the vasospasm, definitive clipping of the aneurysms was performed on Day 13 post embolization. One patient had a good clinical recovery and was discharged without neurological deficit. The other patient's hospital course was complicated by the occurrence of a postoperative posterior temporal infarct requiring partial temporal lobectomy, although she eventually had a good recovery with only a small visual field deficit. Based on data obtained in these two patients, one can infer that ruptured wide-necked MCA aneurysms associated with severe local vasospasm may best be treated using a staged combined treatment plan. Delayed clip application might be performed more safely 4 to 6 weeks postocclusion, or later, than at 2 weeks.

Clinical utility of quantitative magnetic resonance angiography in the assessment of the underlying pathophysiology in a variety of cerebrovascular disorders.

BACKGROUND: Quantitative MRA (qMRA) is a relatively new technique that uses traditional time-of-flight and phase-contrast MRI to visualize extracranial and intracranial vascular anatomy and measure volumetric blood flow. We aimed to assess the clinical utility of qMRA in assessing the hypothesized pathophysiology (HP) in a range of cerebrovascular diseases. Moreover, we postulated that evaluation of the arterial waveforms, can improve the evaluation of the hypothesized pathophysiology by qMRA. METHODS: We reviewed studies from 10 patients who underwent qMRA examinations before and after their treatments. Two reviewers assessed the anatomy, volumetric flow rates and arterial waveforms for each vessel sampled and reached a consensus as to whether the above parameters supported the clinical diagnosis/hypothesized pathophysiology and the subsequent management. FINDINGS: All 20 qMRA studies were technically adequate. qMRA supported the HP in all 10 patients as determined by abnormal volumetric flow values in the affected vessels before treatment and by the correction of these abnormal values in the patients whose treatment was successful. Each of our five patients with occlusive disease/vasoconstriction demonstrated evidence of dampening of the arterial waveforms distally to the narrowed artery (parvus-tardus phenomenon). The parvus-tardus effect disappeared after treatment. CONCLUSION: qMRA is unique in combining time-of-flight MRA in a complementary manner with phase-contrast MRA to obtain volumetric flow values and potentially important physiologic information from arterial waveform analysis in patients with a range of cerebrovascular diseases during the course of a single MR examination.

Contrast extravasation on computed tomographic angiography mimicking a basilar artery aneurysm in angiogram-negative subarachnoid hemorrhage: report of 2 cases.

BACKGROUND AND IMPORTANCE: Contrast extravasation on computed tomography angiography (CTA) is becoming more common, with increasing use of CTA for myriad intracranial vascular pathologies. This article describes the first 2 documented cases of contrast extravasation from a nonaneurysmal basilar artery source seen on CTA and discusses possible pathophysiologic mechanisms. CLINICAL PRESENTATION: We present 2 cases of diffuse atraumatic subarachnoid hemorrhage in which the CTA showed an abnormality in association with the basilar artery highly suggestive of a ruptured aneurysm. Follow-up digital subtraction angiography, however, was completely negative. Subsequent repeat digital subtraction angiography failed to reveal a vascular lesion. Both patients were treated for complications associated with SAH, but given the negative digital subtraction angiography, no intervention was performed. CONCLUSION: Because of the frequent use of CTA, contrast extravasation is an increasingly common observation. Physicians should be aware that basilar artery extravasation can mimic the appearance of an aneurysm.