Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial Chronic Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Loss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level-dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared. MATERIALS AND METHODS: Patients (n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level-dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement. RESULTS: Extensive leptomeningeal collateral circulation was present in all cases. Decreased concordance between the methods was found in vascular territories with stenosis distal to but not proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed low concordance. A model of multiple temporally displaced arterial inputs from leptomeningeal collateral flow demonstrated that the resultant lengthening MTT mimicked compromised hemodynamic reserve despite being sufficient to support blood oxygenation level-dependent contrast. CONCLUSIONS: Decreased concordance between the 2 methods for assessment of hemodynamic reserve for vascular disease distal to the circle of Willis is posited to be due to well-developed leptomeningeal collateral circulation providing multiple temporally displaced arterial input functions that bias the perfusion analysis toward hemodynamic reserve compromise while blood oxygenation level-dependent activation remains detectable.

Clearance of Subarachnoid Hemorrhage from the Cerebrospinal Fluid in Computational and In Vitro Models.

Subarachnoid hemorrhage (SAH) mostly occurs following the rupture of cerebral aneurysm causing blood to leak into the cranial subarachnoid space (SAS). Hemorrhage volume has been linked to the development of secondary vasospasm. Therefore, eliminating blood contaminants from the cerebrospinal fluid (CSF) space after the initial hemorrhage could improve patient outcomes and prevent the development of vasospasm. A number of clinical trials demonstrate that lumbar drainage effectively clears hemorrhagic debris from the cranial compartment. The benefits of optimal lumbar drainage rate and patient orientation are difficult to determine by trial-and-error in live patients, because of the invasive nature, limited subject availability and ethical considerations. Therefore, there is a lack of consensus about clinical guidelines for the use of continuous lumbar drainage following the ictus of SAH. A realistic bench-top model which reproduces the anatomy and CSF dynamics of the human central nervous system (CNS) was built to experimentally study contaminant clearance scenarios under lumbar drainage. To mimic a hemorrhagic event, porcine blood was injected at the basal cistern level of the bench-top model and the efficacy of lumbar drains was assessed experimentally for different drainage rates and patient orientations. In addition, the efficacy of blood clearance was predicted with a computational fluid dynamics (CFD) model. Bench-top experiments and CFD simulations identify body position and drainage rates as key parameters for effective blood clearance. The study findings suggest the importance of treatment in upright position to maximize contaminant diversion from the cranial CSF compartment. The bench-top CNS model together with the validated CFD predictions of lumbar drainage systems can serve to optimize subject-specific treatment options for SAH patients.

Cerebral microcirculation and oxygen tension in the human secondary cortex.

The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm(3) subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection-diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty.

In vivo evaluation of quantitative MR angiography in a canine carotid artery stenosis model.

BACKGROUND AND PURPOSE: Large-vessel cerebral blood flow quantification has emerged as a potential predictor of stroke risk. QMRA uses phase-contrast techniques to noninvasively measure vessel flows. To evaluate the in vivo accuracy of QMRA for measuring the effects of progressive arterial stenosis, we compared this technique with invasive flow measurements from a sonographic transit-time flow probe in a canine model. MATERIALS AND METHODS: A sonographic flow probe was implanted around the CCA of hound dogs (n = 4) under general anesthesia. Pulsatile blood flow and arterial pressure were continuously recorded during CCA flow measurements with QMRA. A vascular tourniquet was applied around the CCA to produce progressive stenosis and varying flow rates. Statistical comparisons were made by using the Pearson product moment correlation coefficient. RESULTS: A total of 60 paired CCA flow measurements were compared. Mean blood flows ranged between 21 and 691 mL/min during QMRA acquisition as measured by the flow probe. The correlation coefficients between flow probe and QMRA measurements for mean, maximum, and minimum volume flow rates were 0.99 (P < .0001), 0.98 (P < .0001), and 0.96 (P < .0001), respectively. The overall proportional difference between the 2 techniques was 7.8 ± 1%. Measurements at higher flow rates and in the absence of arterial stenosis had the lowest PD. CONCLUSIONS: Noninvasive CCA flow measurements by using QMRA are accurate compared with invasive flow-probe measurements in a canine arterial flow model with stenosis and may be useful for the evaluation of the hemodynamic effects of stenosis caused by cerebrovascular atherosclerosis.

Use of cervical spinal cord stimulation in treatment and prevention of arterial vasospasm after aneurysmal subarachnoid hemorrhage. Technical details.

Based on past laboratory and anecdotal clinical experience, we hypothesized that prolonged cervical spinal cord stimulation (SCS) in the acute settings of aneurysmal subarachnoid hemorrhage (aSAH) would be both safe and feasible, and that 2-week stimulation will reduce incidence of cerebral arterial vasospasm. The goal of our clinical study was to establish feasibility and safety of cervical SCS in a small group of selected aSAH patients. Single-arm non-randomized prospective study of cSCS in aSAH patients involved percutaneous implantation of 8-contact electrode in 12 consecutive aSAH patients that satisfied strict inclusion criteria. The electrode insertion was performed immediately upon surgical or endovascular securing of the ruptured aneurysm while the patient was still under general anesthesia. Patients were stimulated for 14 consecutive days or until discharge. There were no complications related to the electrode insertion or to SCS during the study and no long-term side effects of SCS during 1-year follow-up. There was 1 unrelated death and two electrode pullouts. This article summarizes technical details of SCS electrode insertion and the stimulation parameters used in the research study. Our study of SCS for prevention of vasospasm after aSAH conclusively shows both safety and feasibility of this promising treatment approach. Despite high level of acuity in aSAH patients, impaired level of consciousness, frequent patient re-positioning, need in multiple tests and variety of monitors, SCS electrodes may be safely implanted and maintained for the two-week period. Long-term follow up shows no adverse effects of cervical SCS in this patient category.

Double phakomatosis; neurofibromatosis type-1 and tuberous sclerosis.

Neurocutaneous syndromes represent some of the most common inherited disorders of the nervous system. Neurofibromatosis type-1 (NF-1) and tuberous sclerosis are well described. Yet, the presentation of both syndromes in the same patient is quite rare. We performed a thorough review of the literature of such double phakomatosis including pattern of inheritance. Eleven cases were reported in the literature. In addition we report a young patient who presented with clinical picture suggestive of both NF-1 and tuberous sclerosis, and present a radiographic and histopathological description of the case.

Role of temozolomide in spinal cord low grade astrocytomas: results in two paediatric patients.

BACKGROUND: The optimal treatment of low grade intramedullary spinal cord tumours remains controversial. In many cases the tumours continue to progress even after surgery and radiation. Effective chemotherapy may be an important therapeutic adjunct in this setting. Temozolomide is widely used for brain gliomas, yet its role in the management of spinal cord tumours has not been reported. PROCEDURE: Two paediatric patients with low grade spinal cord astrocytomas were diagnosed to have progression of the tumour in spite of surgery and radiotherapy. They received temozolomide, 200 mg/m2 daily for five days every four weeks for 10 cycles, and were followed serially. RESULTS: Stabilization of the spinal tumour in both patients was observed at 18 months of follow-up. One of the patients developed haematological toxicity requiring platelet transfusion and dose reduction. CONCLUSION: Based on our findings in two paediatric patients, temozolomide may be a useful agent in the management of progressive recurrent low grade spinal cord astrocytomas.

Spontaneous subdural haematoma in anabolic steroids dependent weight lifters: reports of two cases and review of literature.

Spontaneous subdural haematoma is very rare in young patients. The complications of anabolic steroid intake in weight lifters are numerous, yet subdural haematomas have not been reported. We report on two cases of spontaneous subdural haematomas in young weight lifters. Both patients underwent surgical evacuation and made a full recovery. A review of the literature on the complications associated with valsalva manoeuvres is also presented including hemodynamic and intracranial changes. We propose that patients on chronic anabolic steroids may have vascular changes that predispose them to bleeding during a Valsalva manoeuvre (VM).