Peter A. Rasmussen

US Multicenter Experience With the Wingspan Stent System for the Treatment of Intracranial Atheromatous Disease: Periprocedural Results

Background and Purpose— The current report details our initial periprocedural experience with Wingspan (Boston Scientific/Target), the first self-expanding stent system designed for the treatment of intracranial atheromatous disease. Methods— All patients undergoing angioplasty and stenting with the Gateway balloon–Wingspan stent system were prospectively tracked. Results— During a 9-month period, treatment with the stent system was attempted in 78 patients (average age, 63.6 years; 33 women) with 82 intracranial atheromatous lesions, of which 54 were ≥70% stenotic. Eighty-one of 82 lesions were successfully stented (98.8%) during the first treatment session. In 1 case, the stent could not be delivered across the lesion; the patient was treated solely with angioplasty and stented at a later date. Lesions treated involved the internal carotid (n=32; 8 petrous, 10 cavernous, 11 supraclinoid segment, 3 terminus), vertebral (n=14; V4 segment), basilar (n=14), and middle cerebral (n=22) arteries. Mean±SD pretreatment stenosis was 74.6±13.9%, improving to 43.5±18.1% after balloon angioplasty and to 27.2±16.7% after stent placement. Of the 82 lesions treated, there were 5 (6.1%) major periprocedural neurological complications, 4 of which ultimately led to patient death within 30 days of the procedure. Conclusions— Angioplasty and stenting for symptomatic intracranial atheromatous disease can be performed with the Gateway balloon–Wingspan stent system with a high rate of technical success and acceptable periprocedural morbidity. Our initial experience indicates that this procedure represents a viable treatment option for this patient population.

Serum S-100β as a possible marker of blood–brain barrier disruption

Two brain-specific proteins, S-100β and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100β levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100β is a marker of blood–brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100β increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100β is an early marker of BBB opening that is not necessarily related to neuronal damage.

Endovascular reconstruction with the Neuroform stent as monotherapy for the treatment of uncoilable intradural pseudoaneurysms.

OBJECTIVE:Intradural pseudoaneurysms have a malignant natural history and can be difficult to treat if parent vessel deconstruction is not feasible. These lesions often involve a long arterial segment and lack a defined saccular component that would safely accommodate the introduction of embolization coils. The current report describes the successful endovascular treatment of these lesions using a strategy of Neuroform stent reconstruction. METHODS:A retrospective review of the prospectively maintained Neuroform databases from our two institutions identified all intracranial aneurysms treated with the Neuroform stent alone, without embolization coils. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS:Over a 38-month study period (10/02–2/06), 266 aneurysms were treated with the Neuroform stent. Of these, 10 were small “uncoilable” intradural pseudoaneurysms associated with subarachnoid hemorrhage. These lesions were treated using a strategy of endovascular stent reconstruction of the diseased vascular segment with one or more Neuroform stents (without concomitant coil embolization). Seven pseudoaneurysms were treated in the context of acute or subacute subarachnoid hemorrhage, and three were associated with a remote history of subarachnoid hemorrhage. Periprocedural complications occurred in two patients (clinically silent, intraprocedural thromboembolic event successfully treated with intra-arterial abciximab, symptomatic postprocedural stent thrombosis with successful thrombolysis, and excellent neurological recovery). Both complications occurred in patients with ruptured aneurysms and could be attributed to inadequate platelet inhibition at the time of the initial procedure. Follow-up conventional angiographic examinations were available for all 10 patients with pseudoaneurysms (1–18.5 mo; average, 9.0 mo). In nine cases, the aneurysms improved at follow-up, with either complete (n = 5) or near complete (n = 4) resolution. In one case, short-term follow-up (1 mo) demonstrated no significant change. No patient has rehemorrhaged after treatment. CONCLUSION:Endovascular Neuroform stent reconstruction represents an optimal strategy for the management of intradural pseudoaneurysms that require a constructive treatment strategy and are too small to accommodate the introduction of embolization coils. Nine out of 10 patients in the current series treated with this strategy demonstrated some degree of endovascular remodeling with either complete (n = 5) or partial (n = 4) angiographic resolution at follow-up. No rehemorrhages were encountered. Adequate antiplatelet therapy, even in the setting of acute subarachnoid hemorrhage, is prerequisite for the avoidance of thromboembolic complications.

Outcome after the Treatment of Spinal Dural Arteriovenous Fistulae: A Contemporary Single-institution Series and Meta-analysis

OBJECTIVE:Spinal dural arteriovenous fistulae (Type I spinal AVMs) are the most common type of spinal vascular malformations. The optimal treatment strategy has yet to be defined, and endovascular embolization is being offered with increasing frequency. A 7-year single-institution retrospective review of outcome with surgical management of Type I spinal AVMs is presented along with a meta-analysis of existing literature. METHODS:For the institutional analysis, a retrospective review of all patients who underwent treatment at our institution for Type I spinal AVMs was performed. Between 1995 and the present (the time frame during which endovascular treatments were available), 19 consecutive patients were treated. Follow-up was performed by clinical examination or telephone interview, and functional status was measured by use of the Aminoff-Logue score. For the meta-analysis, a MEDLINE search between 1966 and the present was performed for surgical, endovascular, or combined treatment of spinal dural arteriovenous fistula. These series were included in a meta-analysis to evaluate success and failure rates, complications, and functional outcome. Specifically, embolization and microsurgery were compared. RESULTS:For the institutional analysis, 18 of 19 patients were available for long-term follow-up after surgery. There were no surgical failures, but one complication was seen. Patients demonstrated a statistically significant improvement in gait and bladder function after surgery. For the meta-analysis, 98% of those patients treated with microsurgery had their dural arteriovenous fistulae successfully obliterated after the initial treatment, compared with only 46% with embolization, as judged by radiographic or clinical follow-up. 89% percent of patients demonstrated improvement or stabilization in neurological symptoms after surgical treatment. Few complications were demonstrated with either surgery or embolization. CONCLUSION:At this point, surgery seems to be superior to embolization for the management of spinal dural arteriovenous fistula. The fistula is usually obliterated after the initial treatment, with few clinical or radiographic recurrences. The majority of patients either improve or stabilize after treatment. Few worsen, and the morbidity is minimal. It is reasonable to attempt initial embolization, especially at the time of the initial diagnostic spinal angiogram. The treating physicians and patients should be aware of the high chance of recurrence, and patients may ultimately require surgery or repeat embolization. After endovascular therapy, patients are committed to repeat angiography and probably embolization. For these reasons, it is the authors’ opinion that surgery should be used as the first-line therapy for spinal dural arteriovenous fistulae.

Wingspan in-stent restenosis and thrombosis: Incidence, clinical presentation, and management

OBJECTIVE: Wingspan (Boston Scientific, Fremont, CA) is a self-expanding stent designed specifically for the treatment of symptomatic intracranial atheromatous disease. The current series reports the observed incidence of in-stent restenosis (ISR) and thrombosis on angiographic follow-up. METHODS: A prospective, intent-to-treat registry of patients in whom the Wingspan stent system was used to treat symptomatic intracranial atheromatous disease was maintained at five participating institutions. Clinical and angiographic follow-up results were recorded. ISR was defined as stenosis greater than 50% within or immediately adjacent (within 5 mm) to the implanted stents and absolute luminal loss greater than 20%. RESULTS: To date, follow-up imaging (average duration, 5.9 mo; range, 1.5-15.5 mo) is available for 84 lesions treated with the Wingspan stent (78 patients). Follow-up examinations consisted of 65 conventional angiograms, 17 computed tomographic angiograms, and two magnetic resonance angiograms. Of these lesions with follow-up, ISR was documented in 25 and complete thrombosis in four. Two of the 4 patients with stent thrombosis had lengthy lesions requiring more than one stent to bridge the diseased segment. ISR was more frequent (odds ratio, 4.7; 95% confidence intervals, 1.4-15.5) within the anterior circulation (42%) than the posterior circulation (13%). Of the 29 patients with ISR or thrombosis, eight were symptomatic (four with stroke, four with transient ischemic attack) and 15 were retreated. Of the retreatments, four were complicated by clinically silent in-stent dissections, two of which required the placement of a second stent. One was complicated by a postprocedural reperfusion hemorrhage. CONCLUSION: The ISR rate with the Wingspan stent is higher in our series than previously reported, occurring in 29.7% of patients. ISR was more frequent within the anterior circulation than the posterior circulation. Although typically asymptomatic (76% of patients in our series), ISR can cause neurological symptoms and may require target vessel revascularization.OBJECTIVEWingspan (Boston Scientific, Fremont, CA) is a self-expanding stent designed specifically for the treatment of symptomatic intracranial atheromatous disease. The current series reports the observed incidence of in-stent restenosis (ISR) and thrombosis on angiographic follow-up. METHODSA prospective, intent-to-treat registry of patients in whom the Wingspan stent system was used to treat symptomatic intracranial atheromatous disease was maintained at five participating institutions. Clinical and angiographic follow-up results were recorded. ISR was defined as stenosis greater than 50% within or immediately adjacent (within 5 mm) to the implanted stents and absolute luminal loss greater than 20%. RESULTSTo date, follow-up imaging (average duration, 5.9 mo; range, 1.5–15.5 mo) is available for 84 lesions treated with the Wingspan stent (78 patients). Follow-up examinations consisted of 65 conventional angiograms, 17 computed tomographic angiograms, and two magnetic resonance angiograms. Of these lesions with follow-up, ISR was documented in 25 and complete thrombosis in four. Two of the 4 patients with stent thrombosis had lengthy lesions requiring more than one stent to bridge the diseased segment. ISR was more frequent (odds ratio, 4.7; 95% confidence intervals, 1.4–15.5) within the anterior circulation (42%) than the posterior circulation (13%). Of the 29 patients with ISR or thrombosis, eight were symptomatic (four with stroke, four with transient ischemic attack) and 15 were retreated. Of the retreatments, four were complicated by clinically silent in-stent dissections, two of which required the placement of a second stent. One was complicated by a postprocedural reperfusion hemorrhage. CONCLUSIONThe ISR rate with the Wingspan stent is higher in our series than previously reported, occurring in 29.7% of patients. ISR was more frequent within the anterior circulation than the posterior circulation. Although typically asymptomatic (76% of patients in our series), ISR can cause neurological symptoms and may require target vessel revascularization.

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Influence of Patient Age and Stenosis Location on Wingspan In-Stent Restenosis

BACKGROUND AND PURPOSE: Wingspan is a self-expanding, microcatheter-delivered microstent specifically designed for the treatment of symptomatic intracranial atherosclerotic disease. Our aim was to discuss the effect of patient age and lesion location on in-stent restenosis (ISR) rates after percutaneous transluminal angioplasty and stenting (PTAS) with the Wingspan system. MATERIALS AND METHODS: Clinical and angiographic follow-up results were recorded for all patients from 5 participating institutions. ISR was defined as >50% stenosis within or immediately adjacent (within 5 mm) to the implanted stent and >20% absolute luminal loss. For the present analysis, patients were stratified into younger (≤55 years) and older (>55 years) age groups. RESULTS: ISR occurred at a rate of 45.2% (14/31) in the younger group and 24.2% (15/62) in the older group (odds ratio, 2.6; 95% confidence interval, 1.03–6.5). In the younger group, ISR occurred after treatment of 13/26 (50%) anterior circulation lesions versus only 1/5 (20%) posterior circulation lesions. In the older group, ISR occurred in 9/29 (31.0%) anterior circulation lesions and 6/33 (18.2%) posterior circulation lesions. In young patients, internal carotid artery lesions (10/17 treated, 58.8%), especially those involving the supraclinoid segment (8/9, 88.9%), were very prone to ISR. When patients of all ages were considered, supraclinoid segment lesions had much higher rates of both ISR (66.6% versus 24.4%) and symptomatic ISR (40% versus 3.9%) in comparison with all other locations. CONCLUSION: Post-Wingspan ISR is more common in younger patients. This increased risk can be accounted for by a high prevalence of anterior circulation lesions in this population, specifically those affecting the supraclinoid segment, which are much more prone to ISR and symptomatic ISR than all other lesions.

Y-configured dual intracranial stent-assisted coil embolization for the treatment of wide-necked basilar tip aneurysms

OBJECTIVE:Despite advances in both the surgical and endovascular treatment of intracranial aneurysms, wide-necked basilar tip aneurysms (i.e., basilar tip aneurysms in which both posterior cerebral arteries emanate from the base of a wide-necked aneurysm) represent a subset of aneurysms that continues to pose technical challenges in treatment. We sought to demonstrate the safety and short-term durability of a novel dual stent-assisted coil embolization technique. METHODS:Two Neuroform stents (Boston Scientific/Target, Fremont, CA) were deployed in the posterior cerebral arteries and the basilar artery, one passing through the interstices of the other in a Y-configuration, thereby recreating an aneurysm neck and enabling safe coil delivery while preserving the parent vessels. RESULTS:Seven patients with unruptured, asymptomatic, wide-necked basilar tip aneurysms involving both posterior cerebral arteries and ranging in size from 7 to 20 mm underwent treatment with this stent-assisted coiling technique. Two stents were successfully deployed in six of the patients and one stent was successfully deployed in the seventh. One patient developed a transient internuclear ophthalmoplegia, and another experienced transient partial right oculomotor nerve palsy. All aneurysms had complete or near-complete embolization with the initial procedure. Follow-up angiography performed 6 months (six patients) and 1 year (one patient) after treatment demonstrated coil compaction and slight recanalization in one patient and recanalization requiring retreatment in another. All patients were neurologically intact at least 6 months after the initial procedure, as well as subsequent procedures, without clinical signs of subarachnoid hemorrhage. CONCLUSION:These initial technical and clinical results are highly encouraging, and this technique may significantly improve the endovascular treatment of intracranial aneurysms.

Cutaneous Vasoconstriction Affects Near-infrared Spectroscopy Determined Cerebral Oxygen Saturation during Administration of Norepinephrine

Background: Perioperative optimization of spatially resolved near-infrared spectroscopy determined cerebral frontal lobe oxygenation (scO2) may reduce postoperative morbidity. Norepinephrine is routinely administered to maintain cerebral perfusion pressure and, thereby, cerebral blood flow, but norepinephrine reduces the scO2. We hypothesized that norepinephrine-induced reduction in scO2 is influenced by cutaneous vasoconstriction. Methods: Fifteen healthy male subjects (25 ± 5 yr, mean ± SD) were studied during: hyperventilation (1.5 kPa end-tidal PcO2 reduction), whole-body heating, administration of norepinephrine (0.15 &mgr;g · kg−1 · min−1; with and without end-tidal carbon dioxide correction), and hypoxia (FiO2: 0.12%). Arterial (saO2), skin, and internal jugular venous oxygen saturations (sjO2) were recorded, and the average cerebral capillary oxygen saturation (scapO2) was calculated. Results: This study indicates that scO2 is influenced by skin oxygen saturation because whole-body heating increased scO2 by 3.6% (2.1–5.1%; 95% CI) and skin oxygen saturation by 3.1% (1.3–4.9%), whereas scapO2 remained unaffected. Conversely, hyperventilation decreased scO2 by 2.1% (0.4–3.7%) and scapO2 by 5.3% (3.8–6.9%), whereas skin oxygen saturation increased 1.8% (0.5–3.1%). In response to hypoxia, scO2 (10.2%; 6.6–13.7%), scapO2 (7.9%; 6.4–9.4%), and skin oxygen saturation (8.9%; 6.3–11.6%) all decreased. With administration of norepinephrine there was a 2.2% (1.0–4.3%) decrease in skin oxygen saturation and scO2 decreased 6.2% (4.2–8.0%), with scapO2 remaining unaffected. Conclusion: The results confirm that spatially resolved near-infrared spectroscopy detects cerebral deoxygenation with systemic hypoxic exposure and hyperventilation. However, a commonly used vasopressor norepinephrine disturbs skin oxygen saturation to an extent that influences scO2.

Angiographic patterns of Wingspan in-stent restenosis.

OBJECTIVE A classification system developed to characterize in-stent restenosis (ISR) after coronary percutaneous transluminal angioplasty with stenting was modified and applied to describe the appearance and distribution of ISR occurring after Wingspan (Boston Scientific, Fremont, CA) intracranial percutaneous transluminal angioplasty with stenting. METHODS A prospective, intention-to-treat, multicenter registry of Wingspan treatment for symptomatic intracranial atherosclerotic disease was maintained. Clinical and angiographic follow-up results were recorded. ISR was defined as greater than 50% stenosis within or immediately adjacent (within 5 mm) to the implanted stent(s) and greater than 20% absolute luminal loss. ISR lesions were classified by angiographic pattern, location, and severity in comparison with the original lesion treated. RESULTS Imaging follow-up (3-15.5 months) was available for 127 intracranial stenotic lesions treated with Wingspan percutaneous transluminal angioplasty with stenting. Forty-one lesions (32.3%) developed either ISR (n = 36 [28.3%]) or complete stent occlusion (n = 5 [3.9%]) after treatment. When restenotic lesions were characterized using the modified classification system, 25 of 41 (61.0%) were focal lesions involving less than 50% of the length of the stented segment: three were Type IA (focal stenosis involving one end of the stent), 21 were Type IB (focal intrastent stenosis involving a segment completely contained within the stent), and one was Type IC (multiple noncontiguous focal stenoses). Eleven lesions (26.8%) demonstrated diffuse stenosis (>50% of the length of the stented segment): nine were Type II with diffuse intrastent stenosis (completely contained within the stent) and two were Type III with proliferative ISR (extending beyond the stented segment). Five stents were completely occluded at follow-up (Type IV). Of the 36 ISR lesions, 16 were less severe or no worse than the original lesion with respect to severity of stenosis or length of the segment involved; 20 lesions were more severe than the original lesion with respect to the segment length involved (n = 5), actual stenosis severity (n = 6), or both (n = 9). Nine of 10 supraclinoid internal carotid artery ISR lesions and nine of 13 middle cerebral artery ISR lesions were more severe than the original lesion. CONCLUSION Wingspan ISR typically occurs as a focal lesion. In more than half of ISR cases, the ISR lesion was more extensive than the original lesion treated in terms of lesion length or stenosis severity. Supraclinoid internal carotid artery and middle cerebral artery lesions have a propensity to develop more severe posttreatment stenosis.