The safety of dedicated-team catheter-based diagnostic cerebral angiography in the era of advanced noninvasive imaging.

BACKGROUND AND PURPOSE: Given the current high quality and usefulness of noninvasive cerebrovascular imaging, invasive angiographic evaluation of the cerebrovascular system is justified if the procedural risk for a neurologic complication is far below the anticipated benefit. The purpose of this study was to evaluate the safety of diagnostic cerebral angiography provided by a dedicated neurointerventional team in a high-volume university hospital. MATERIALS AND METHODS: A consecutive cohort of 1715 patients undergoing diagnostic cerebral angiography at our institution from 2000 to 2008 was retrospectively assessed for incidence of stroke or TIA related to cerebral angiography. In the subgroup of patients (n = 40) who serendipitously underwent DWI within the first 30 days after cerebral angiography, the presence of new DWI hyperintensities found in territories explored during angiography was tabulated. Complications related to the catheter technique and sheath placement were also studied. RESULTS: No stroke or permanent neurologic deficit was seen in any of the 1715 patients undergoing diagnostic neuroangiography. One patient experienced a TIA. Nonneurologic complications without long-term sequelae occurred in 9 patients. Two patients had punctate areas of restricted diffusion in territories that had been angiographically explored. CONCLUSIONS: Within a high-volume neurointerventional practice, the risk for neurologic complications related to catheter-based diagnostic cerebral angiography can approach zero. As the absolute number of invasive diagnostic procedures diminishes with time, diagnostic cerebral angiography remains a useful tool while providing a foundation for neuroendovascular interventions, and should preferably be performed in institutions with high-volume operators also capable of managing unanticipated complicating adverse events.

Preoperative selective internal carotid artery dural branch embolisation for petroclival meningiomas.

We assessed the clinical value of preoperative embolisation of the dural branches of the internal carotid artery (ICA) in cases of petroclival meningioma was evaluated. We carried out preoperative selective embolisation on seven consecutive patients with large petroclival meningiomas, using nonbraided 2 F steam-shaped microcatheters and shapeable hydrophilic microguide-wires to enter the dural branches of the ICA. The embolisations were performed using digital subtraction fluoroscopy with 150-250 microm polyvinyl alcohol particles. The tumours were resected a few days after embolisation. We reviewed angiographic findings before and after endovascular devascularisation, blood loss during tumour resection and clinical outcome. All endovascular procedures were technically successful, and postembolisation angiography showed disappearance of or marked decrease in tumour stain in all cases. Intraoperative bleeding was easily controlled, and intraoperative blood loss was low.

Rheolytic thrombectomy of the occluded internal carotid artery in the setting of acute ischemic stroke.

BACKGROUND AND PURPOSE: Acute thromboembolic stroke complicated by ipsilateral carotid occlusion may present both mechanical and inflow-related barriers to effective intracranial thrombolysis. We sought to review our experience with a novel method of mechanical thrombectomy, in such cases, using the Possis AngioJet system, a rheolytic thrombectomy device. METHODS: A review of our interventional neuroradiology database revealed three patients in whom an occluded cervical internal carotid artery was encountered during endovascular treatment for acute stroke and in whom thrombectomy was attempted, using the 5F Possis AngioJet thrombectomy catheter. The medical records and radiographic studies of these patients were reviewed. RESULTS: Three patients were identified (ages, 52--84 years). Two patients had isolated occlusion of the internal carotid artery; in one patient, thrombus extended down into the common carotid artery. Treatment was initiated within 190 to 360 minutes of stroke onset. Thrombectomy of the carotid artery was deemed necessary because of poor collateral flow to the affected hemisphere (chronic contralateral internal carotid artery occlusion [one patient] and thrombus extending to the carotid "T" [one patient]) or inability to pass a microcatheter through the occluded vessel (one patient). Adjunctive therapy included pharmacologic thrombolysis with tissue plasminogen activator (all patients), carotid angioplasty and stenting (two patients), and middle cerebral artery angioplasty (one patient). Patency of the carotid artery was reestablished in two patients, with some residual thrombus burden. In the third patient, the device was able to create a channel through the column of thrombus, allowing intracranial access. CONCLUSION: Rheolytic thrombectomy shows potential for rapid, large-burden thrombus removal in cases of internal carotid artery thrombosis, allowing expedient access to the intracranial circulation for additional thrombolytic therapy.

Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: prospective study applying diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Aneurysm embolization using Guglielmi detachable coils (GDC) is gaining increasing acceptance as a viable alternative to surgery in the treatment of cerebral aneurysms. Although recent reports describe a significant rate of symptomatic thromboembolic complications with GDC use, many of the neurologic deficits are transient. We sought to determine the incidence of silent thromboembolic events with the use of diffusion-weighted imaging and to correlate radiologic findings with the results of neurologic examinations. METHODS: Diffusion-weighted MR imaging was performed within 48 hours in 14 consecutive elective GDC aneurysm treatments. Embolizations were performed under systemic heparinization; all flush solutions were heparinized, and both guiding catheters and microcatheters were placed for continuous heparinized infusions. Neurologic examination, including the National Institutes of Health Stroke Scale determination, was performed by a stroke neurologist before the coiling procedures were performed, immediately after the procedures were performed, and before discharge. MR imaging examinations were reviewed by a stroke neurologist and an interventional neuroradiologist, with determination and characterization of diffusion-weighted imaging abnormalities. RESULTS: Small areas of restricted diffusion, presumed to represent procedure-related embolic infarctions, were noted on the images of eight of 14 patients. All except one of the areas were located ipsilateral to the side of the catheterization. Six patients had evidence of multiple infarcts. Most lesions were small (<2 mm); one patient with coil stretch and herniation into the parent vessel had numerous infarcts with a dominant posterior frontal infarct. Pre- and posttreatment National Institutes of Health Stroke Scale scores were unchanged for 13 of 14 patients. Overall, the rate of asymptomatic emboli was 61% (eight of 13 treatments) in uncomplicated treatments. Strokes occurred independently of the number of coils used; the mean number of coils used for patients with strokes was 7.6 (range, two to 13) and for patients without evidence of infarcts was 10.2 (range, one to 30). This was not a significant difference (P > .5). CONCLUSION: Silent thromboembolic events related to the use of the GDC system are a common occurrence, despite meticulous technique and systemic anticoagulation. Although clinical sequelae are rare, the high rate of occurrence suggests that alterations in the technique, such as the addition of antiplatelet agents, should be considered.

Videographic assessment of the embolic characteristics of three polymeric compounds: ethylene vinyl alcohol, cellulose acetate, and liquid urethane.

BACKGROUND AND PURPOSE: Aneurysms have been clinically and experimentally treated with various surgical and endovascular methods, including endovascular polymer instillation. Additional tools may help to identify advantages and disadvantages of polymeric aneurysm treatment. We assessed the value of high-resolution videography to compare in vitro embolization characteristics of ethylene vinyl alcohol copolymer (VIN), cellulose acetate polymer (ACE), and urethane copolymer (UCO). METHODS: In a "neck-up" glass aneurysm model, solutions of 8% and 12% VIN, 8% and 12% ACE, and 8% UCO were introduced through a microcatheter into a xanthan gum solution at three flow rates: full physiological (62 cm/s), half physiological, and flow arrest. Each formulation was then introduced into a "neck-down" aneurysm model at flow arrest, for a total of 20 experiments. Results were tabulated for six different categories: outflow tail formation, inflow-zone polymer-mass deformation, inflow-zone migration, detachment tail formation, adherent mass pullout, and conjectural net effect. RESULTS: Of the 20 experiments, nine had unacceptable results because of potential clinical complications. The results were unacceptable in four of eight VIN experiments, four of eight ACE experiments, and one of four UCO experiments. VIN performance was more dependent on flow arrest than the more viscous ACE. The growth of the ACE solutions was most circumferential, with balloonlike growth characteristics, little inflow-zone effects, and fewer outflow tails than seen with VIN. All compounds had the potential for partial catheter adhesion and catheter-adhesing tails. UCO had the highest percentage of favorable results and the lowest percentage of unfavorable results. CONCLUSION: Videographic analysis allows detailed assessment of the dynamic embolization characteristics of polymers, revealing potential advantages of compounds such as UCO.

Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke.

BACKGROUND: Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients. OBJECTIVE: To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke. DESIGN: A prospective cohort study. SETTING: A referral center. PATIENTS AND METHODS: Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps. MAIN OUTCOME MEASURES: Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences. RESULTS: Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI. CONCLUSION: During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients.

OBJECTIVE: To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI. METHODS: MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute. RESULTS: The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old. CONCLUSION: In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

Sonography, CT, and MR imaging: a prospective comparison of neonates with suspected intracranial ischemia and hemorrhage.

BACKGROUND AND PURPOSE: Sonography, CT, and MR imaging are commonly used to screen for neonatal intracranial ischemia and hemorrhage, yet few studies have attempted to determine which imaging technique is best suited for this purpose. The goals of this study were to compare sonography with CT and MR imaging prospectively for the detection of intracranial ischemia or hemorrhage and to determine the prognostic value(s) of neuroimaging in neonates suspected of having hypoxic-ischemic injury (HII). METHODS: Forty-seven neonates underwent CT (n = 26) or MR imaging (n = 24) or both (n = 3) within the first month of life for suspected HII. Sonography was performed according to research protocol within an average of 14.4 +/- 9.6 hours of CT or MR imaging. A kappa analysis of interobserver agreement was conducted using three independent observers. Infants underwent neurodevelopmental assessment at ages 2 months (n = 47) and 2 years (n = 26). RESULTS: CT and MR imaging had significantly higher interobserver agreement (P < .001) for cortical HII and germinal matrix hemorrhage (GMH) (Grades I and II) compared with sonography. MR imaging and CT revealed 25 instances of HII compared with 13 identified by sonography. MR imaging and CT also revealed 10 instances of intraparenchymal hemorrhage (>1 cm, including Grade IV GMH) compared with sonography, which depicted five. The negative predictive values of neuroimaging, irrespective of technique used, were 53.3% and 58.8% at the 2-month and 2-year follow-up examinations, respectively. CONCLUSION: CT and MR imaging have significantly better interobserver agreement for cortical HII and GMH/intraventricular hemorrhage and can reveal more instances of intraparenchymal hemorrhage compared with sonography. The absence of neuroimaging findings on sonograms, CT scans, or MR images does not rule out later neurologic dysfunction.

Basilar artery stenosis: clinical and neuroradiographic features.

INTRODUCTION: Although basilar artery stenosis (BAS) is an important cause of posterior circulation stroke, few reports detail the clinical and neuroradiological features of patients with BAS. METHODS: A retrospective review of symptomatic BAS patients who were evaluated by our Stroke Center. RESULTS: Twenty-eight patients were followed-up for a median of 16 months. Transient ischemic attacks (TIAs) specific for posterior circulation involvement were common (12/19 patients with TIA), were often multiple, and frequently preceded a posterior circulation stroke. The proximal (13/28) and mid (10/28) basilar arteries were the most common sites of stenosis. Brain infarction most often affected the pons, but also frequently involved the cerebellum and thalamus. Concomitant vertebral artery disease was prevalent (12/18 patients who underwent conventional cerebral angiography). Stroke mechanisms included artery to artery embolus, basilar branch disease, and hypoperfusion. The same-territory recurrent stroke rate was 8.2% per year. Most patients in the series were treated with warfarin. No patients suffered a recurrent stroke while on a therapeutic dose of warfarin (international normalized ratio [INR], 2.0 to 3.0). Angioplasty was performed in 6 patients. CONCLUSIONS: The same-territory stroke recurrence rate was 8.2% per year. Warfarin (INR, 2.0 to 3.0) appeared to be effective in preventing recurrent strokes. Angioplasty of the basilar artery was technically feasible. Symptomatic BAS typically affected the proximal and mid-basilar artery and most often caused infarction in the pons. The mechanisms for stroke were heterogeneous. TIAs frequently preceded a posterior circulation stroke.

Intracystic hemorrhage of the middle fossa arachnoid cyst and subdural hematoma caused by ruptured middle cerebral artery aneurysm.

We report a case of a cerebral aneurysm arising from the bifurcation of the left middle cerebral artery that ruptured into a left middle cranial fossa arachnoid cyst, associated with acute subdural hematoma. We discuss the relationships of aneurysm, arachnoid cyst, and subdural hematoma.

Joint motion in an open MR unit using MR tracking.

A system for active scan plane guidance during kinematic magnetic resonance (MR) examination of joint motion was developed utilizing an external tracking coil and MR tracking software. In a phantom study and during upright, weight-bearing, physiologic knee flexion, the external tracking coil maintained the scan plane through desired structures. Thus, MR tracking provides a robust method to guide the scan plane during MR imaging of active joint motion.

Outcome of angioplasty for atherosclerotic intracranial stenosis.

BACKGROUND AND PURPOSE: We sought to assess the long-term outcome and efficacy of percutaneous transluminal angioplasty in the treatment of symptomatic intracranial atherosclerotic stenoses. METHODS: Twenty-three patients with fixed symptomatic intracranial stenoses were treated over a 5-year period with percutaneous transluminal angioplasty. Patients who underwent successful angioplasty were followed up for 16 to 74 months (mean, 35.4 months). RESULTS: An angioplasty that resulted in decreased stenosis was performed in 21 of 23 patients (91.3%). In 1 case a stenosis could not be safely crossed, and in another balloon dilatation resulted in vessel rupture. This vessel rupture resulted in the 1 periprocedural death in the series. In follow-up there was 1 stroke in the same vascular territory as the angioplasty and 2 strokes in the series overall. This yielded an annual stroke rate of 3.2% for strokes in the territory appropriate to the site of angioplasty. CONCLUSIONS: Intracranial angioplasty can be performed with a high degree of technical success. The long-term clinical follow-up available in this series suggests that it may reduce the risk of future stroke in patients with symptomatic intracranial stenoses.

Management of biopsy needle artifacts: techniques for RF-refocused MRI.

Several methods were investigated to improve the depiction of biopsy needles in radiofrequency (RF)-refocused magnetic resonance imaging. Distortion correction is performed by the use of view angle tilting (VAT): a gradient is employed on the slice-select axis during readout. Needle conspicuity is increased by offsetting the gradient echo from the spin echo and by inverting the 90 degrees RF pulse slice-select gradient. VAT effectively re-registers in-plane shifts. Since this method changes the projection angle through the slice, some structures appear blurred, while other structures appear sharper. VAT does not correct errors in slice selection. Offsetting the spin echo from the gradient echo increases needle conspicuity but can result in a shift in the apparent location of the needle. Inverting the 90 degrees slice-select gradient effectively increases the needle conspicuity with no shift in the needle location. These methods provide an easy and interactive means to manipulate needle artifacts but should be used cautiously.

Embolization of basal ganglia and thalamic arteriovenous malformations.

OBJECTIVE: Basal ganglia and thalamic arteriovenous malformations (AVMs) show a poor natural history and have proven difficult to treat. We report the safety and efficacy of presurgical and preradiosurgical embolization of these deep central lesions and describe the contribution of embolization to multimodality treatment. METHODS: Thirty-eight patients with basal ganglia and/or thalamic AVMs underwent embolization in a total of 69 sessions. Seven of the 38 patients (18.4%) presented with hemorrhage, and 23 of 38 (60.5%) exhibited neurological deficits before therapy. Thirty patients (78.9%) underwent embolization with a liquid adhesive (cyanoacrylate), and five of these patients also underwent embolization with polyvinyl alcohol. Five patients (13.2%) were treated with polyvinyl alcohol or polyvinyl alcohol and silk. One patient (2.6%) underwent embolization alone, 19 (50.0%) underwent embolization followed by radiosurgery, 5 (13.2%) underwent embolization plus microsurgical resection, and 13 (34.2%) patients were treated using all three modalities. RESULTS: Three patients did not undergo embolization because of the morphological features of the AVMs and poor endovascular access. The patients who underwent embolization achieved AVM volume reductions of 10 to 100% (mean, 49.7%). Fifteen patients (39.5%) achieved complete obliteration of their AVMs, one with embolization alone, three with embolization followed by radiosurgery, five with embolization plus microsurgical resection, and six with a combination of all three modalities. At the time of the last follow-up imaging session, embolization combined with radiosurgery (19 patients) yielded a mean volume reduction of 81.1%, and all three modalities (13 patients) yielded a mean reduction of 84.6%. Four permanent neurological deficits resulted from embolization (5.8% of procedures, 10.5% of patients). The embolization-related complication rate was higher in the earlier years (1984-1989) of this series. CONCLUSION: Endovascular embolization plays an important role in multimodality treatment of AVMs involving the basal ganglia and/or thalamus. Embolization can result in obliteration of a significant volume of the AVM and may allow complete obliteration of the AVM when combined with microsurgical resection and/or stereotactic radiosurgery.

Percutaneous transfemoral embolization of an indirect carotid-cavernous fistula with cortical venous access to the cavernous sinus. Case report.

The authors present the case of a 61-year-old man with an indirect carotid-cavernous fistula (CCF). Many now advocate a primary transvenous approach to deal with such lesions, with packing and thrombosis of the cavernous sinus leading to fistula obliteration. Transvenous access to the cavernous sinus via the inferior petrosal sinus is the usual route of access; both surgical and transfemoral superior ophthalmic vein approaches are also well described. In the case presented, the anatomy of the CCF was unfavorable for these approaches and its dominant venous egress was via a single enlarged arterialized cortical vein. The cavernous sinus was accessed with a transfemoral retrograde approach to the cortical draining vein. Successful CCF embolization was documented radiographically and clinically. To the authors' knowledge, this procedure has not been previously described in the English literature.

MRI abnormalities associated with partial status epilepticus.

OBJECTIVE: To report neuroimaging findings in patients with complex partial status epilepticus. BACKGROUND: During status epilepticus, neuroimaging may be used to exclude other neurologic conditions. Therefore, it is important to identify the neuroimaging features that are associated with status epilepticus. In addition, MRI characteristics may provide insight into the pathophysiologic changes during status epilepticus. METHODS: The history and neuroimaging examination results of three patients with complex partial status epilepticus were reviewed. Studies obtained during status epilepticus included diffusion-weighted MRI (DWI), MR angiography (MRA), postcontrast T1-weighted MRI, T2-weighted MRI, and CT. Follow-up MRI was obtained in two patients, and autopsy results were available for the third. RESULTS: Some of the MRI and CT findings during partial status epilepticus mimicked those of acute ischemic stroke: DWI and T2-weighted MRI showed cortical hyperintensity with a corresponding low apparent diffusion coefficient, and CT showed an area of decreased attenuation with effacement of sulci and loss of gray-white differentiation. However, the lesions did not respect vascular territories, there was increased signal of the ipsilateral middle cerebral artery on MRA, and leptomeningeal enhancement appeared on postcontrast MRI. On follow-up imaging, the abnormalities had resolved, but some cerebral atrophy was present. CONCLUSIONS: The radiologic characteristics of status epilepticus resemble those of ischemic stroke but can be differentiated based on lesion location and findings on MRA and postcontrast MRI. The MRI abnormalities indicated the presence of cytotoxic and vasogenic edema, hyperperfusion of the epileptic region, and alteration of the leptomeningeal blood-brain barrier. These changes reversed, but they resulted in some regional brain atrophy.

Embolization of rolandic cortex arteriovenous malformations.

OBJECTIVES: To evaluate the safety and efficacy of preradiosurgical and presurgical embolization of arteriovenous malformations (AVMs) involving the rolandic cortex. METHODS: Seventeen consecutive patients with rolandic AVMs seen during a 31-month period (December 1994-July 1997) were evaluated. All patients underwent superselective sodium amobarbital testing to determine any changes in the results of the neurological examinations before undergoing embolization. In 16 of 17 patients (94.1%), somatosensory evoked potentials augmented physical examinations. Patients were embolized with N-butyl cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and iophendylate (Ethiodol; Savage Labs, Melville, NY). Rigid control of the mean arterial pressure (65-75 mm Hg) was maintained in all patients for 24 to 48 hours after embolization. RESULTS: Twenty-three embolization sessions were performed in 17 patients (mean, 1.5 sessions/patient), and a total of 40 feeding arteries were embolized. Two patients were unable to undergo embolization because of positive results of the amobarbital testing despite repeated attempts to reposition a microcatheter in the AVM circulation. In one case, somatosensory evoked potentials and the results of the physical examination were both positive; in the other case, only the somatosensory evoked potentials were used (in a pediatric patient under general anesthesia). All patients with AVMs that were embolized experienced a significant size reduction of their lesions (range, 20-95%; mean, 63%). There were no permanent complications. Four procedures (10% of the procedures, 23% of the patients) resulted in minor transient neurological deficits, with patients' conditions returning to baseline. Thirteen patients subsequently underwent radiosurgery, three underwent surgical resection, and one underwent combined surgery and radiosurgery. Complete obliteration of the lesions has been achieved in four patients to date (three who underwent surgery and one who underwent radiosurgery), with the remainder undergoing further follow-up. CONCLUSION: When properly evaluated before treatment, rolandic AVMs can be embolized with a high success rate (measured by completed embolization and size reduction) and a low complication rate.

Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI.

BACKGROUND: Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined. CASE DESCRIPTION: The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused. CONCLUSIONS: Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.

Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus.

OBJECTIVE: The host immune response and low vector efficiency have been key impediments to effective cystic fibrosis transmembrane regulator (CFTR) gene transfer for cystic fibrosis (CF). An adeno-associated virus vector (AAV-CFTR) was used in a phase I dose-escalation study to transfer CFTR cDNA into respiratory epithelial cells of the maxillary sinus of 10 CF patients. STUDY DESIGN: A prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of AAV-CFTR was conducted. PATIENTS: Ten patients with previous bilateral maxillary antrostomies were treated. MAIN OUTCOME MEASURES: Safety, gene transfer as measured by semiquantitative polymerase chain reaction (PCR), and sinus transepithelial potential difference (TEPD) were measured. RESULTS: The highest level of gene transfer was observed in the range of 0.1-1 AAV-CFTR vector copy per cell in biopsy specimens obtained 2 weeks after treatment. When tested, persistence was observed in one patient for 41 days and in another for 10 weeks. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. Little or no inflammatory or immune responses were observed. CONCLUSION: AAV-CFTR administration to the maxillary sinus results in successful, dose-dependent gene transfer to the maxillary sinus and alterations in sinus TEPD suggestive of a functional effect, with little or no cytopathic or host immune response. Further study is warranted for AAV vectors as they may prove useful for CFTR gene transfer and other in vivo gene transfer therapies. A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF.

Maxillary sinusitis as a surrogate model for CF gene therapy clinical trials in patients with antrostomies.

BACKGROUND: Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy. One problem with pulmonary surrogate markers of CF disease is the large number of patients and length of time required to demonstrate clinical efficacy. An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease. Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology. METHODS: Sinusitis recurrence in untreated sinuses was analyzed during a prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator (AAV-CFTR) gene transfer. RESULTS: Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence. Sinusitis recurred at a rate of 45% during one month of follow-up. IL-8 concentration rose in sinus fluids from affected sinuses. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. Sinus CT scans were also useful in diagnosing recurrent sinusitis in this surrogate model of CF infectious exacerbations. CONCLUSIONS: CF sinusitis as a surrogate for lung disease is particularly well-suited for phase II clinical trials of gene transfer agents, with the potential for measuring clinical efficacy in relatively small numbers of patients over relatively short periods of time.