✓ Selective intraarterial infusion of papaverine is used in the treatment of symptomatic cerebral vasospasm. The authors report two episodes of severe thrombocytopenia in a patient that were related to intraarterial administration of papaverine. A 70-year-old man with a right internal carotid artery aneurysm underwent craniotomy and aneurysm clipping. He became lethargic 8 days after the hemorrhage occurred. Cerebral angiography revealed moderate vasospasm. In addition to hypervolemic—hypertensive therapy, the patient was treated on two occasions with intraarterial administration of papaverine. Within 24 hours of both treatments he developed severe thrombocytopenia. On one occasion epistaxis requiring transfusion of blood products occurred. Laboratory data support the diagnosis of immune-mediated papaverine-induced thrombocytopenia. The authors conclude that intraarterial administration of papaverine for treatment of vasospasm can be associated with severe, rapidly reversible thrombocytopenia.
Janice A. Miller, DeWitte T. Cross, Christopher J. Moran, Ralph G. Dacey Jr., Janice G. McFarland and Michael N. Diringer
James M. Milburn, Christopher J. Moran, DeWitte T. Cross III, Michael N. Diringer, Thomas K. Pilgram and Ralph G. Dacey Jr.
Object. This study was conducted to determine if there is a change in intracranial arterial diameters after papaverine infusion for vasospasm and to determine whether the change occurs in proximal, intermediate, and distal arteries.
Methods. The authors measured arterial diameters retrospectively in all patients who received intraarterial papaverine for treatment of vasospasm between November 1992 and August 1995. Patients who received papaverine in the same session with or following angioplasty were excluded. Measurements were made in a blinded manner with the aid of a magnification loupe at 12 predetermined sites on each angiogram before and after papaverine infusion. Eighty-one treatments in 34 patients were included. Angiograms obtained at the time of presentation with subarachnoid hemorrhage (SAH) were examined in 26 of the 34 patients. Nine carotid territories visualized by repeated angiography on the day after infusion were examined to determine the duration of the papaverine effect.
Conclusions. In all treatment groups an increase was found in the average arterial diameters ranging from 2.8 to 73.9%, with a mean increase of 26.5%. Increases in diameter were observed in proximal, intermediate, and distal arteries. The timing of treatments ranged from Day 3 to Day 19 post-SAH, and there was no relationship between timing and arterial responsiveness (r = −0.06). There was a moderately good correlation between the degree of vasospasm in an artery and its responsiveness to papaverine (r = −0.54, −0.66, and −0.66, for proximal, intermediate, and distal arteries, respectively). The effect of papaverine did not persist until the following day in patients in whom repeated angiography was performed.
Colin P. Derdeyn, DeWitte T. Cross III, Christopher J. Moran, George W. Brown, Thomas K. Pilgram, Michael N. Diringer, Robert L. Grubb Jr., Keith M. Rich, Michael R. Chicoine and Ralph G. Dacey Jr.
Object. Ischemic stroke or transient ischemic attack (TIA) may occur after the treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The purpose of the present study is to investigate possible risk factors for thromboembolic events and to determine their frequency and time course.
Methods. The records of 178 consecutive patients with 193 treated intracranial saccular aneurysms were reviewed. A total of 159 GDC procedures were performed to treat 143 aneurysms in 133 of those patients who were in good neurological condition, allowing clinical detection of postprocedure ischemic events (TIA or stroke). The association of clinical, anatomical, and pharmacological factors with intraprocedure intraarterial thrombus and with postprocedure ischemic events was investigated by using uni- and multivariate analyses.
Thrombus protruding into the parent artery was noted during six of 159 GDC procedures, resulting in a clinical deficit in one patient. No factor was associated with intraprocedure intraarterial thrombus. Ten postprocedure ischemic events occurred in nine patients. Seven events occurred within 24 hours, and three events occurred between 24 hours and 58 days. Aneurysm diameter and protruding coils were significant independent predictors of postprocedure ischemic events in multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%.
Conclusions. Larger aneurysm diameter and protruding loops of coils are associated with postprocedure ischemic events after GDC placement. It is unlikely that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.
Chad W. Washington, Gregory J. Zipfel, Michael R. Chicoine, Colin P. Derdeyn, Keith M. Rich, Christopher J. Moran, DeWitte T. Cross and Ralph G. Dacey Jr.
The purpose of aneurysm surgery is complete aneurysm obliteration while sparing associated arteries. Indocyanine green (ICG) videoangiography is a new technique that allows for real-time evaluation of blood flow in the aneurysm and vessels. The authors performed a retrospective study to compare the accuracy of ICG videoangiography with intraoperative angiography (IA), and determine if ICG videoangiography can be used without follow-up IA.
From June 2007 through September 2009, 155 patients underwent craniotomies for clipping of aneurysms. Operative summaries, angiograms, and operative and ICG videoangiography videos were reviewed. The number, size, and location of aneurysms, the ICG videoangiography and IA findings, and the need for clip adjustment after ICG videoangiography and IA were recorded. Discordance between ICG videoangiography and IA was defined as ICG videoangiography demonstrating aneurysm obliteration and normal vessel flow, but post-IA showing either an aneurysmal remnant and/or vessel occlusion requiring clip adjustment.
Thirty-two percent of patients (49 of 155) underwent both ICG videoangiography and IA. The post-ICG videoangiography clip adjustment rate was 4.1% (2 of 49). The overall rate of ICG videoangiography–IA agreement was 75.5% (37 of 49) and the ICG videoangiography–IA discordance rate requiring post-IA clip adjustment was 14.3% (7 of 49). Adjustments were due to 3 aneurysmal remnants and 4 vessel occlusions. These adjustments were attributed to obscuration of the residual aneurysm or the affected vessel from the field of view and the presence of dye in the affected vessel via collateral flow. Although not statistically significant, there was a trend for ICG videoangiography–IA discordance requiring clip adjustment to occur in cases involving the anterior communicating artery complex, with an odds ratio of 3.3 for ICG videoangiography–IA discordance in these cases.
These results suggest that care should be taken when considering ICG videoangiography as the sole means for intraoperative evaluation of aneurysm clip application. The authors further conclude that IA should remain the gold standard for evaluation during aneurysm surgery. However, a combination of ICG videoangiography and IA may ultimately prove to be the most effective strategy for maximizing the safety and efficacy of aneurysm surgery.
Manish N. Shah, James A. Botros, Thomas K. Pilgram, Christopher J. Moran, DeWitte T. Cross III, Michael R. Chicoine, Keith M. Rich, Ralph G. Dacey Jr., Colin P. Derdeyn and Gregory J. Zipfel
The goal of this study was to determine the clinical course of Borden-Shucart Type I cranial dural arteriovenous fistulas (DAVFs) and to calculate the annual rate of conversion of these lesions to more aggressive fistulas that have cortical venous drainage (CVD).
A retrospective chart review was conducted of all patients harboring DAVFs who were seen at the authors' institution between 1997 and 2009. Twenty-three patients with Type I DAVFs who had available clinical follow-up were identified. Angiographic and clinical data from these patients were reviewed. Neurological outcome and status of presenting symptoms were assessed during long-term follow-up.
Of the 23 patients, 13 underwent endovascular treatment for intolerable tinnitus or ophthalmological symptoms, and 10 did not undergo treatment. Three untreated patients died of unrelated causes. In those who were treated, complete DAVF obliteration was achieved in 4 patients, and palliative reduction in DAVF flow was achieved in 9 patients. Of the 19 patients without radiographic cure, no patient developed intracranial hemorrhage or nonhemorrhagic neurological deficits (NHNDs), and no patient died of DAVF-related causes over a mean follow-up of 5.6 years. One patient experienced a spontaneous, asymptomatic obliteration of a partially treated DAVF in late follow-up, and 2 patients experienced a symptomatic conversion of their DAVF to a higher-grade fistula with CVD in late follow-up. The annual rate of conversion to a higher-grade DAVF based on Kaplan-Meier cumulative event-free survival analysis was 1.0%. The annual rate of intracranial hemorrhage, NHND, and DAVF-related death was 0.0%.
A small number of Type I DAVFs will convert to more aggressive DAVFs with CVD over time. This conversion to a higher-grade DAVF is typically heralded by a change in patient symptoms. Follow-up vascular imaging is important, particularly in the setting of recurrent or new symptoms.
Josser E. Delgado Almandoz, Bharathi D. Jagadeesan, Daniel Refai, Christopher J. Moran, DeWitte T. Cross III, Michael R. Chicoine, Keith M. Rich, Michael N. Diringer, Ralph G. Dacey Jr., Colin P. Derdeyn and Gregory J. Zipfel
The yield of CT angiography (CTA) and MR angiography (MRA) in patients with subarachnoid hemorrhage (SAH) who have a negative initial catheter angiogram is currently not well understood. This study aims to determine the yield of CTA and MRA in a prospective cohort of patients with SAH and a negative initial catheter angiogram.
From January 1, 2005, until September 1, 2010, the authors instituted a prospective protocol in which patients with SAH—as documented by noncontrast CT or CSF xanthochromia and a negative initial catheter angiogram— were evaluated using CTA and MRA to assess for causative cerebral aneurysms. Two neuroradiologists independently evaluated the noncontrast CT scans to determine the SAH pattern (perimesencephalic or not) and the CT and MR angiograms to assess for causative cerebral aneurysms.
Seventy-seven patients were included, with a mean age of 52.8 years (median 54 years, range 19–88 years). Fifty patients were female (64.9%) and 27 male (35.1%). Forty-three patients had nonperimesencephalic SAH (55.8%), 29 patients had perimesencephalic SAH (37.7%), and 5 patients had CSF xanthochromia (6.5%). Computed tomography angiography demonstrated a causative cerebral aneurysm in 4 patients (5.2% yield), all of whom had nonperimesencephalic SAH (9.3% yield). Mean aneurysm size was 2.6 mm (range 2.1–3.3 mm). Magnetic resonance angiography demonstrated only 1 of these aneurysms. No causative cerebral aneurysms were found in patients with perimesencephalic SAH or CSF xanthochromia.
Computed tomography angiography is a valuable adjunct in the evaluation of patients with nonperimesencephalic SAH who have a negative initial catheter angiogram, demonstrating a causative cerebral aneurysm in 9.3% of patients.
Ananth K. Vellimana, Yasha Kadkhodayan, Keith M. Rich, DeWitte T. Cross III, Christopher J. Moran, Allyson R. Zazulia, Jin-Moo Lee, Michael R. Chicoine, Ralph G. Dacey Jr., Colin P. Derdeyn and Gregory J. Zipfel
The aim of this study was to define the optimal treatment for patients with symptomatic intraluminal carotid artery thrombus (ICAT).
The authors performed a retrospective chart review of patients who had presented with symptomatic ICAT at their institution between 2001 and 2011.
Twenty-four patients (16 males and 8 females) with ICAT presented with ischemic stroke (18 patients) or transient ischemic attack ([TIA], 6 patients). All were initially treated using anticoagulation with or without antiplatelet drugs. Eight of these patients had no or only mild carotid artery stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography; of these, 10 underwent delayed revascularization (8 patients, carotid endarterectomy [CEA]; 2 patients, angioplasty and stenting), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs after treatment. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation therapy, either during the perioperative period or in the long-term follow-up; 1 patient died of an unrelated condition. The mean follow-up was 16.4 months.
Results of this study suggest that initial anticoagulation for symptomatic ICAT leads to a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner.
Chad W. Washington, Colin P. Derdeyn, Rajat Dhar, Eric J. Arias, Michael R. Chicoine, DeWitte T. Cross, Ralph G. Dacey Jr., Byung Hee Han, Christopher J. Moran, Keith M. Rich, Ananth K. Vellimana and Gregory J. Zipfel
Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients.
A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as “improvement” or “no improvement” in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms.
Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0–2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%–200%).
The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.