A Comparison of Diffusion-Weighted Imaging Abnormalities Following Balloon Remodeling for Aneurysm Coil Embolization in the Ruptured vs Unruptured Setting

A Comparison of Diffusion-Weighted Imaging Abnormalities Following Balloon Remodeling for... Abstract BACKGROUND The prothrombotic milieu seen in subarachnoid hemorrhage (SAH) poses a unique challenge to neurovascular surgeons with regard to device use and microcatheter practice. OBJECTIVE To determine how demographic factors and balloon practices impact diffusion-weighted imaging (DWI) abnormalities and outcomes in patients with SAH compared to those without (non-SAH). METHODS We retrospectively analyzed 77 patients with SAH treated by balloon-assisted coiling in a single institution compared with 81 consecutive patients with unruptured aneurysms treated by balloon-assisted coiling at the same institution. Data were collected with regard to demographic factors, procedural and anatomic considerations, and DWI abnormalities on postprocedural magnetic resonance imaging. RESULTS SAH patients were significantly more likely to have DWI abnormality (75% vs 21%, P < .0001) and had a higher number and volume of DWI (4.0 vs 3.0, P = .0421 and 1.3 vs 0.3 cc, P = .0041) despite similar balloon practices. SAH patients were not more likely to have DWI abnormality in vascular territory distal to the treated aneurysm but had a higher likelihood of DWI in a vascular territory unrelated to the aneurysm (81.5% vs 47.1%, P = .0235). Patients without DWI abnormality were significantly more likely to have a good outcome as defined by modified Rankin Score 0 to 2 (95.6% vs 81.6%, P = .0328). Patients with DWI abnormality more often underwent 4-vessel angiography (70.5% vs 48.0%, P = .0174), but this was not found to be significant on multivariate analysis. CONCLUSION Balloon-assisted coiling does not result in increased incidence of downstream ischemic events in SAH patients compared to non-SAH patients and is safe in this cohort of patients. Other factors, such as 4-vessel angiography of the SAH milieu itself, may predispose patients to a higher rate of ischemic events. Subarachnoid hemorrhage, Diffusion-weighted imaging ABBREVIATIONS ABBREVIATIONS CI confidence interval DWI diffusion-weighted imaging MRI magnetic resonance imaging mRS modified Rankin Score OR odds ratio SAH subarachnoid hemorrhage Subarachnoid hemorrhage (SAH) is a morbid disease affecting as many as 30 000 patients per year in the United States, with ruptured intracranial aneurysm being responsible for approximately 80% of these cases.1 Evidence exists to support the notion that aneurysmal SAH incites a systemic proinflammatory state. There is a volume of evidence that proinflammatory markers are seen in the blood and cerebrospinal fluid following SAH.2,3 Additionally, it is thought that this proinflammatory state also induces a prothrombotic state immediately following aneurysmal SAH,4,5,6 and that prothrombotic markers are significantly higher in poor-grade SAH patients.7 Endovascular coiling is rapidly becoming standard of care for the majority of patients with intracranial aneurysms indicated for treatment, and the technique of balloon-assisted coiling has become commonplace in cases of geometrically difficult aneurysms not amenable to standard embolization techniques. In general, the recent literature to date supports balloon-assisted coiling as safe and effective,8,9 although the balloon technique has been associated with increased complications in an isolated series of SAH patients.10 We present a group of patients with and without SAH who underwent balloon-assisted coil embolization, analyzing number, volume, and location of diffusion abnormalities on magnetic resonance imaging (MRI) between the 2 groups with regard to balloon inflation practice and demographic factors. METHODS A retrospective chart review was undertaken of 77 consecutive patients with aneurysmal SAH in which the index aneurysm was treated by balloon remodeling at a single institution, a metropolitan tertiary care facility. Standard institutional practice for SAH patients was followed, including comanagement by neurosurgery and neurocritical care and aneurysm treatment within 24 h via a “coil-first” policy. All patients underwent a 4-vessel angiogram per protocol. This study was approved by the institutional review board. A group of 81 consecutive patients (previously reported)11 with unruptured aneurysms treated by balloon remodeling over the same time period at the same institution serve as an internal control group. Demographics Data were collected by the senior author (AMS) with respect to age, gender, history of hypertension, history of diabetes, history of tobacco usage, previous stroke, and antiplatelet (ie, use of aspirin, clopidogrel, or both) use in both groups. Procedural and Anatomic Considerations All patients underwent digital subtraction angiography under general endotracheal anesthesia in the neuroangiography suite. Blood pressure was maintained with a goal systolic blood pressure <140 mm Hg and mean arterial pressure >65 mm Hg, and was not pharmacologically augmented during balloon inflations. Patients were classified as having a 4-vessel angiogram if they underwent a full diagnostic cerebral angiogram prior to their intervention, as opposed to a case in which only the vessel of interest was selected. With respect to balloon inflation practice, total procedural time, cumulative balloon inflation time, number of balloon inflations, average and maximum single inflation times, and total and maximum times deflated were recorded for each patient in minutes and seconds. Intraprocedural heparin was administered prior to insertion of guide catheter in all patients in both groups. In general, the standard guide catheters used at the treating institution were either a 6-French Envoy or a 0 to 70 Neuron catheter. The balloon was either a Hyperglide or Hyperform. An SL-10 catheter was preferred as an access catheter. The number, size, and type of coil was variable based on the individual morphology of each aneurysm. If individual patient circumstance demanded, other materials could be used. Imaging All patients in both the SAH and the no-SAH group were protocolled to undergo postprocedural MRI within 24 h of procedure, but owing to logistical factors, 44 patients in the SAH group were not able to undergo the scan within the allotted window. These images were reviewed by a single reviewer for location and volume of abnormal diffusion-weighted imaging (DWI) signal using the technique as described by Sims et al.12 The reviewer was blinded with regard to treatment for each imaging study. DWI abnormalities were categorized as either being in a vascular territory distal to the aneurysm or in a vascular territory unrelated to the aneurysm (“other”). Radiographic review was performed by a single, independent reviewer who was blinded to treatment. Outcome DWI lesions were classified as symptomatic if they were associated with a neurological deficit referable to the anatomic area of the lesion, or as asymptomatic. A modified Rankin Score (mRS) was assessed at most recent follow-up or at 90 d (whichever was later), and patients were stratified according to mRS 0 to 2 or mRS 3 to 6. Statistical Analysis Statistical analyses were performed using SAS Version 9.3 (SAS Institute, Cary, North Carolina). A population of 158 subjects was analyzed using descriptive statistics to characterize injury type, balloon procedures, and procedural complications and outcomes. Differences between groups were tested using a chi-square test for categorical measures or Fisher's exact test for categorical measures with expected cell sizes under 5. Differences between groups were assessed using the paired t-test or analysis of variance for normally distributed continuous measures. Balloon practices and number and volume of DWI were compared across 2 groups using the Wilcoxon signed rank test and across 3 groups using the Kruskal–Wallis test due to nonnormally distributed data. The correlation between total inflation time, number of inflations, maximum single inflation, mean inflation, and inflation downtime with volume and number of DWI was assessed using Spearman rank correlation. Finally, a multivariate analysis was performed, as described in the Results section. All tests were assessed at a significance level of 0.05. RESULTS A total of 158 patients were treated with balloon remodeling and are included in this study. Seventy-seven patients (57% female, aged 54 ± 13 yr) underwent coil embolization of a ruptured cerebral aneurysm with balloon remodeling (SAH group). Eighty-one patients (88% female; aged 57 ± 12 yr) underwent coil embolization of an unruptured cerebral aneurysm with balloon remodeling in the elective setting (no-SAH group). Table 1 shows the comparison data between the SAH and no-SAH groups. TABLE 1. Population Comparison Between Subarachnoid and Nonsubarachnoid Subjects (n = 158)   n  SAH (n = 77)  No SAH (n = 81)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Gender  158      <.0001   Female    44 (57.1%)  72 (88.9%)     Male    33 (42.9%)  9 (11.1%)    Age (years)  158  54.6 (13.8)  57.6 (12.4)  .1651  Hypertension  158  33 (42.9%)  41 (50.6%)  .3285  Diabetes  158  8 (10.4%)  10 (12.4%)  .6989  Tobacco  158      .0301   Current    44 (57.1%)  33 (40.7%)     Remote    9 (11.7%)  22 (27.2%)     None    24 (31.2%)  26 (32.1%)    Antiplatelets  158  27 (35.1%)  51 (63.0%)  .0005  Previous stroke  158  1 (1.3%)  15 (18.5%)  .0003  4-vessel angiogram  158  74 (96.1%)  32 (39.5%)  <.0001  Intraprocedural heparin anticoagulation  158  77 (100.0%)  81 (100.0%)  1.0  Pharmacological neuroprotection  158  0 (0.0%)  1 (1.2%)  1.0  Aneurysm location  157         Internal carotid artery    7 (9.1%)  11 (13.8%)  .4549   Posterior communicating artery    11 (14.3%)  14 (17.5%)  .5821   Anterior communicating artery    33 (42.9%)  5 (6.3%)  <.0001   Middle cerebral artery    3 (3.9%)  7 (8.8%)  .3285   Basilar    7 (9.1%)  11 (13.8%)  .4549   Othera    16 (20.8%)  32 (40.0%)  .0090  Procedure times           Total procedural time (min)  120  28.7 (36.5)  36.6 (26.0)  .1961   Total balloon inflation (min)  120  12.3 (14.3)  19.2 (11.7)  .0047   Balloon inflations  123  3.3 (2.4)  4.2 (2.5)  .0689   Average single inflation (min)  120  4.8 (6.6)  5.0 (2.6)  .8459   Maximum single inflation (min)  120  6.5 (8.3)  7.6 (4.3)  .3700   Total time down (min)b  99  21.8 (30.5)  19.7 (15.8)  .6967   Maximum time down (min)b  99  14.3 (20.4)  8.8 (5.6)  .1233  DWI in vascular territory distal to aneurysmc    18 (66.7%)  15 (88.2%)  .1585  DWI in other territoryc    22 (81.5%)  8 (47.1%)  .0235  Overall DWI rate  117  27 (75.0%)  17 (21.0%)  <.0001    n  SAH (n = 77)  No SAH (n = 81)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Gender  158      <.0001   Female    44 (57.1%)  72 (88.9%)     Male    33 (42.9%)  9 (11.1%)    Age (years)  158  54.6 (13.8)  57.6 (12.4)  .1651  Hypertension  158  33 (42.9%)  41 (50.6%)  .3285  Diabetes  158  8 (10.4%)  10 (12.4%)  .6989  Tobacco  158      .0301   Current    44 (57.1%)  33 (40.7%)     Remote    9 (11.7%)  22 (27.2%)     None    24 (31.2%)  26 (32.1%)    Antiplatelets  158  27 (35.1%)  51 (63.0%)  .0005  Previous stroke  158  1 (1.3%)  15 (18.5%)  .0003  4-vessel angiogram  158  74 (96.1%)  32 (39.5%)  <.0001  Intraprocedural heparin anticoagulation  158  77 (100.0%)  81 (100.0%)  1.0  Pharmacological neuroprotection  158  0 (0.0%)  1 (1.2%)  1.0  Aneurysm location  157         Internal carotid artery    7 (9.1%)  11 (13.8%)  .4549   Posterior communicating artery    11 (14.3%)  14 (17.5%)  .5821   Anterior communicating artery    33 (42.9%)  5 (6.3%)  <.0001   Middle cerebral artery    3 (3.9%)  7 (8.8%)  .3285   Basilar    7 (9.1%)  11 (13.8%)  .4549   Othera    16 (20.8%)  32 (40.0%)  .0090  Procedure times           Total procedural time (min)  120  28.7 (36.5)  36.6 (26.0)  .1961   Total balloon inflation (min)  120  12.3 (14.3)  19.2 (11.7)  .0047   Balloon inflations  123  3.3 (2.4)  4.2 (2.5)  .0689   Average single inflation (min)  120  4.8 (6.6)  5.0 (2.6)  .8459   Maximum single inflation (min)  120  6.5 (8.3)  7.6 (4.3)  .3700   Total time down (min)b  99  21.8 (30.5)  19.7 (15.8)  .6967   Maximum time down (min)b  99  14.3 (20.4)  8.8 (5.6)  .1233  DWI in vascular territory distal to aneurysmc    18 (66.7%)  15 (88.2%)  .1585  DWI in other territoryc    22 (81.5%)  8 (47.1%)  .0235  Overall DWI rate  117  27 (75.0%)  17 (21.0%)  <.0001  SAH, subarachnoid hemorrhage; DWI, diffusion-weighted imaging abnormality. aOther includes A1/A2, ophthalmic, posterior inferior cerebellar artery (PICA); superior cerebellar artery (SCA); superior hypophyseal artery (SHA); vertebral, and pericallosal. bSixteen subjects had a single-balloon inflation. cNineteen subjects had a DWI in both the vascular and other territory. They are shown in both groups. View Large Patient Risk Factors: Comorbidities No significant differences were identified between the 2 groups with regard to age, history of hypertension, or history of diabetes. SAH patients were more likely to be female (42.9% vs 11.1%; P < .0001) and have a history of tobacco use (57% vs 40%; P = .03) compared to those with unruptured aneurysms. Significantly more patients in the no-SAH group were on antiplatelet agents than the SAH patients (63% vs 35%; P = .0005). Procedural Factors and Balloon Inflation All patients in both groups underwent intraprocedural heparin anticoagulation with an identical initial bolus and activated clogging time goal, which was 2.5 times the baseline partial thromboplastin time. Heparin was administered prior to guide catheter placement. SAH patients were more likely to undergo a complete diagnostic cerebral angiogram at the time of treatment of the index aneurysm than no-SAH patients; however, total procedural times did not significantly differ between the 2 groups. Total number of balloon inflations, the average single inflation time, maximum single inflation time, total time deflated, and minimum time deflated did not differ between the 2 groups. However, SAH patients were treated with a significantly lower cumulative balloon inflation time compared to the no-SAH patients (12.3 ± 14.3 vs 19.2 ± 11.7 min; P = .0047). DWI Abnormalities SAH patients were more likely to have a DWI abnormality of any type, in any territory, on postprocedural MRI compared to no-SAH patients (75% vs 21%; P < .0001). Grouping all patients (Table 2) demonstrates that patients with DWI were more likely to be male, have undergone a 4-vessel angiogram, and been treated for an anterior communicating artery aneurysm. Among SAH patients alone, no differences were encountered on either demographic, procedural, or anatomic factors among patients with DWI abnormalities compared to those in whom no DWI were found on postprocedure MRI (Table 3). Among no-SAH patients, history of diabetes was significantly higher in those with DWI abnormality as compared to those without (Table 4). TABLE 2. Demographic Comparison between Cohorts with and without DWI Abnormality     No DWI (n = 73)  DWI (n = 44)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0187     Female  63 (86.3%)  30 (68.2%)       Male  10 (13.7%)  14 (31.8%)      Age (years)  55.9 (12.6)  58.3 (13.2)  .3369    Hypertension  34 (46.6%)  22 (50.0%)  .7194    Diabetes  6 (8.2%)  7 (15.9%)  .2325    Tobacco      .2561     Current  30 (41.1%)  25 (56.8%)       Remote  18 (24.7%)  8 (18.2%)       None  25 (34.3%)  11 (25.0%)      Antiplatelets  46 (63.0%)  19 (43.2%)  .0365    Previous stroke  12 (16.4%)  3 (6.8%)  .1617  Anatomic factors  Aneurysm location           Internal carotid artery  10 (13.9%)  3 (6.8%)  .3648     Posterior communicating artery  10 (13.9%)  8 (18.2%)  .6011     Anterior communicating artery  8 (11.1%)  17 (38.6%)  .0008     Middle cerebral artery  7 (9.7%)  0 (0.0%)  .0433     Basilar  9 (12.5%)  4 (9.1%)  .7638     Other  28 (38.9%)  12 (27.8%)  .2015    Circulation           Anterior  60 (82.2%)  36 (81.8%)  .9593     Posterior  13 (17.8%)  8 (18.2%)      Type      .7227     Proximal  60 (82.2%)  35 (79.6%)       Distal  13 (17.8%)  9 (20.5%)    Procedural factors  4-vessel angiogram  35 (48.0%)  31 (70.5%)  .0174    Intraprocedural heparin Anticoagulation  73 (100.0%)  44 (100.0%)  1.0    Pharmacological neuroprotection  1 (1.4%)  0 (0.0%)  1.0    Total procedural time (min)  35.3 (28.5)  29.2 (29.3)  .3133    Total balloon inflation (min)  18.8 (14.3)  14.3 (11.4)  .1096    Balloon inflations  3.8 (2.5)  3.8 (2.5)  .8784    Average single inflation (min)  5.7 (5.4)  4.2 (3.1)  .1061    Maximum single inflation (min)  8.3 (7.6)  6.2 (4.1)  .0757    Total time down (min)  19.3 (17.3)  19.1 (23.4)  .9588    Maximum time down (min)  8.5 (9.7)  7.9 (11.9)  .7815  Outcome  Symptomatic stroke  4 (5.8%)  8 (18.2%)  .0578    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .6249    Modified Rankin scale score (mRS)      .1843     0  44 (64.7%)  20 (52.6%)       1  14 (20.6%)  6 (15.8%)       2  7 (10.3%)  5 (13.2%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.5%)  3 (7.9%)       5  0 (0.0%)  0 (0.0%)       6  2 (2.9%)  4 (10.5%)      mRS 0-2  65 (95.6%)  31 (81.6%)  .0328      No DWI (n = 73)  DWI (n = 44)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0187     Female  63 (86.3%)  30 (68.2%)       Male  10 (13.7%)  14 (31.8%)      Age (years)  55.9 (12.6)  58.3 (13.2)  .3369    Hypertension  34 (46.6%)  22 (50.0%)  .7194    Diabetes  6 (8.2%)  7 (15.9%)  .2325    Tobacco      .2561     Current  30 (41.1%)  25 (56.8%)       Remote  18 (24.7%)  8 (18.2%)       None  25 (34.3%)  11 (25.0%)      Antiplatelets  46 (63.0%)  19 (43.2%)  .0365    Previous stroke  12 (16.4%)  3 (6.8%)  .1617  Anatomic factors  Aneurysm location           Internal carotid artery  10 (13.9%)  3 (6.8%)  .3648     Posterior communicating artery  10 (13.9%)  8 (18.2%)  .6011     Anterior communicating artery  8 (11.1%)  17 (38.6%)  .0008     Middle cerebral artery  7 (9.7%)  0 (0.0%)  .0433     Basilar  9 (12.5%)  4 (9.1%)  .7638     Other  28 (38.9%)  12 (27.8%)  .2015    Circulation           Anterior  60 (82.2%)  36 (81.8%)  .9593     Posterior  13 (17.8%)  8 (18.2%)      Type      .7227     Proximal  60 (82.2%)  35 (79.6%)       Distal  13 (17.8%)  9 (20.5%)    Procedural factors  4-vessel angiogram  35 (48.0%)  31 (70.5%)  .0174    Intraprocedural heparin Anticoagulation  73 (100.0%)  44 (100.0%)  1.0    Pharmacological neuroprotection  1 (1.4%)  0 (0.0%)  1.0    Total procedural time (min)  35.3 (28.5)  29.2 (29.3)  .3133    Total balloon inflation (min)  18.8 (14.3)  14.3 (11.4)  .1096    Balloon inflations  3.8 (2.5)  3.8 (2.5)  .8784    Average single inflation (min)  5.7 (5.4)  4.2 (3.1)  .1061    Maximum single inflation (min)  8.3 (7.6)  6.2 (4.1)  .0757    Total time down (min)  19.3 (17.3)  19.1 (23.4)  .9588    Maximum time down (min)  8.5 (9.7)  7.9 (11.9)  .7815  Outcome  Symptomatic stroke  4 (5.8%)  8 (18.2%)  .0578    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .6249    Modified Rankin scale score (mRS)      .1843     0  44 (64.7%)  20 (52.6%)       1  14 (20.6%)  6 (15.8%)       2  7 (10.3%)  5 (13.2%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.5%)  3 (7.9%)       5  0 (0.0%)  0 (0.0%)       6  2 (2.9%)  4 (10.5%)      mRS 0-2  65 (95.6%)  31 (81.6%)  .0328  View Large TABLE 3. Demographic Comparison of SAH Subjects With and Without DWI Abnormality     No DWI (n = 9)  DWI (n = 27)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .4427     Female  4 (44.4%)  17 (63.0%)       Male  5 (55.6%)  10 (37.0%)      Age (years)  53.7 (14.3)  55.7 (13.9)  .7126    Hypertension  3 (33.3%)  12 (44.4%)  .7050    Diabetes  2 (22.2%)  1 (3.7%)  .1479    Tobacco      .8573     Current  5 (55.6%)  17 (63.0%)       Remote  1 (11.1%)  3 (11.1%)       None  3 (33.3%)  7 (25.9%)      Antiplatelets  4 (44.4%)  10 (37.0%)  .7115    Previous stroke  0 (0.0%)  0 (0.0%)    Anatomic factors  Aneurysm location           Internal carotid artery  0 (0.0%)  2 (7.4%)  1.0     Posterior communicating artery  2 (22.2%)  2 (7.4%)  .2552     Anterior communicating artery  6 (66.7%)  14 (51.9%)  .7003     Middle cerebral artery  0 (0.0%)  0 (0.0%)       Basilar  0 (0.0%)  2 (7.4%)  1.0     Other  1 (11.1%)  7 (25.9%)  .6478    Circulation      .3026     Anterior  9 (100.0%)  21 (77.8%)       Posterior  0 (0.0%)  6 (22.2%)      Type      .3017     Proximal  9 (100.0%)  22 (81.5%)       Distal  0 (0.0%)  5 (18.5%)    Procedural factors  4-vessel angiogram  9 (100.0%)  25 (92.6%)  1.0    Intraprocedural Heparin Anticoagulation  9 (100.0%)  27 (100.0%)      Pharmacological neuroprotection  0 (0.0%)  0 (0.0%)      Total procedural time (min)  33.9 (45.2)  19.9 (29.7)  .3581    Total balloon inflation (min)  18.1 (29.1)  9.2 (8.3)  .4542    Balloon inflations  2.3 (1.0)  3.1 (2.6)  .2696    Average single inflation (min)  8.8 (14.6)  4.2 (3.9)  .4414    Maximum single inflation (min)  12.0 (19.2)  5.6 (5.0)  .4113    Total time down (min)  20.6 (26.6)  16.3 (31.9)  .7846    Maximum time down (min)  19.4 (24.9)  10.8 (18.1)  .4134  Outcome  Symptomatic stroke  1 (20.0%)  6 (22.2%)  1.0    NIHSS (median [IQR])  0.5 (0-1)  0 (0-1)  .7489    Modified Rankin scale score (mRS)      .5704     0  3 (42.9%)  7 (33.3%)       1  1 (14.3%)  3 (14.3%)       2  3 (42.9%)  4 (19.1%)       3  0 (0.0%)  0 (0.0%)       4  0 (0.0%)  3 (14.3%)       5  0 (0.0%)  0 (0.0%)       6  0 (0.0%)  4 (19.1%)      mRS 0-2  7 (100.0%)  14 (66.7%)  .1414      No DWI (n = 9)  DWI (n = 27)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .4427     Female  4 (44.4%)  17 (63.0%)       Male  5 (55.6%)  10 (37.0%)      Age (years)  53.7 (14.3)  55.7 (13.9)  .7126    Hypertension  3 (33.3%)  12 (44.4%)  .7050    Diabetes  2 (22.2%)  1 (3.7%)  .1479    Tobacco      .8573     Current  5 (55.6%)  17 (63.0%)       Remote  1 (11.1%)  3 (11.1%)       None  3 (33.3%)  7 (25.9%)      Antiplatelets  4 (44.4%)  10 (37.0%)  .7115    Previous stroke  0 (0.0%)  0 (0.0%)    Anatomic factors  Aneurysm location           Internal carotid artery  0 (0.0%)  2 (7.4%)  1.0     Posterior communicating artery  2 (22.2%)  2 (7.4%)  .2552     Anterior communicating artery  6 (66.7%)  14 (51.9%)  .7003     Middle cerebral artery  0 (0.0%)  0 (0.0%)       Basilar  0 (0.0%)  2 (7.4%)  1.0     Other  1 (11.1%)  7 (25.9%)  .6478    Circulation      .3026     Anterior  9 (100.0%)  21 (77.8%)       Posterior  0 (0.0%)  6 (22.2%)      Type      .3017     Proximal  9 (100.0%)  22 (81.5%)       Distal  0 (0.0%)  5 (18.5%)    Procedural factors  4-vessel angiogram  9 (100.0%)  25 (92.6%)  1.0    Intraprocedural Heparin Anticoagulation  9 (100.0%)  27 (100.0%)      Pharmacological neuroprotection  0 (0.0%)  0 (0.0%)      Total procedural time (min)  33.9 (45.2)  19.9 (29.7)  .3581    Total balloon inflation (min)  18.1 (29.1)  9.2 (8.3)  .4542    Balloon inflations  2.3 (1.0)  3.1 (2.6)  .2696    Average single inflation (min)  8.8 (14.6)  4.2 (3.9)  .4414    Maximum single inflation (min)  12.0 (19.2)  5.6 (5.0)  .4113    Total time down (min)  20.6 (26.6)  16.3 (31.9)  .7846    Maximum time down (min)  19.4 (24.9)  10.8 (18.1)  .4134  Outcome  Symptomatic stroke  1 (20.0%)  6 (22.2%)  1.0    NIHSS (median [IQR])  0.5 (0-1)  0 (0-1)  .7489    Modified Rankin scale score (mRS)      .5704     0  3 (42.9%)  7 (33.3%)       1  1 (14.3%)  3 (14.3%)       2  3 (42.9%)  4 (19.1%)       3  0 (0.0%)  0 (0.0%)       4  0 (0.0%)  3 (14.3%)       5  0 (0.0%)  0 (0.0%)       6  0 (0.0%)  4 (19.1%)      mRS 0-2  7 (100.0%)  14 (66.7%)  .1414  View Large TABLE 4. Demographic Comparison of Non-SAH Subjects With and Without DWI Abnormality     No DWI (n = 64)  DWI (n = 17)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0868     Female  59 (92.2%)  13 (76.5%)       Male  5 (7.8%)  4 (23.5%)      Age (years)  56.3 (12.4)  62.4 (11.3)  .0656    Hypertension  31 (48.4%)  10 (58.8%)  .4464    Diabetes  4 (6.3%)  6 (35.3%)  .0046    Tobacco      .7821     Current  25 (39.1%)  8 (47.1%)       Remote  17 (26.6%)  5 (29.4%)       None  22 (34.4%)  4 (23.5%)      Antiplatelets  42 (65.6%)  9 (52.9%)  .3357    Previous stroke  12 (18.8%)  3 (17.7%)  1.0  Anatomic factors  Aneurysm location           Internal carotid artery  10 (15.9%)  1 (5.9%)  .4414     Posterior communicating artery  8 (12.7%)  6 (35.3%)  .0649     Anterior communicating artery  2 (3.2%)  3 (17.7%)  .0617     Middle cerebral artery  7 (11.1%)  0 (0.0%)  .3355     Basilar  9 (14.3%)  2 (11.8%)  1.0     Other  27 (42.9%)  5 (29.4%)  .4075    Circulation      .7258     Anterior  51 (79.7%)  15 (88.2%)       Posterior  13 (20.3%)  2 (11.8%)      Type      .7467     Proximal  51 (79.7%)  13 (76.5%)       Distal  13 (20.3%)  4 (23.5%)    Procedural factors  4-vessel angiogram  26 (40.6%)  6 (35.3%)  .6894    Intraprocedural heparin anticoagulation  64 (100.0%)  17 (100.0%)      Pharmacological neuroprotection  1 (1.6%)  0 (0.0%)  1.0    Total procedural time (min)  35.5 (26.2)  40.1 (25.7)  .5222    Total balloon inflation (min)  18.8 (11.7)  20.3 (11.9)  .6687    Balloon inflations  4.0 (2.5)  4.6 (2.2)  .4246    Average single inflation (min)  5.2 (2.8)  4.3 (1.7)  .0990    Maximum single inflation (min)  7.8 (4.7)  6.9 (2.6)  .3186    Total time down (min)  19.2 (16.2)  21.1 (15.1)  .6707    Maximum time down (min)  8.6 (5.2)  9.6 (6.9)  .5199  Outcome  Symptomatic stroke  3 (4.7%)  2 (11.8%)  .2808    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .3882    Modified Rankin scale score      .9502     0  41 (67.2%)  13 (76.5%)       1  13 (21.3%)  3 (17.7%)       2  4 (6.6%)  1 (5.9%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.6%)  0 (0.0%)       5  0 (0.0%)  0 (0.0%)       6  2 (3.3%)  0 (0.0%)      mRS 0-2  58 (95.1%)  17 (100.0%)  1.0      No DWI (n = 64)  DWI (n = 17)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0868     Female  59 (92.2%)  13 (76.5%)       Male  5 (7.8%)  4 (23.5%)      Age (years)  56.3 (12.4)  62.4 (11.3)  .0656    Hypertension  31 (48.4%)  10 (58.8%)  .4464    Diabetes  4 (6.3%)  6 (35.3%)  .0046    Tobacco      .7821     Current  25 (39.1%)  8 (47.1%)       Remote  17 (26.6%)  5 (29.4%)       None  22 (34.4%)  4 (23.5%)      Antiplatelets  42 (65.6%)  9 (52.9%)  .3357    Previous stroke  12 (18.8%)  3 (17.7%)  1.0  Anatomic factors  Aneurysm location           Internal carotid artery  10 (15.9%)  1 (5.9%)  .4414     Posterior communicating artery  8 (12.7%)  6 (35.3%)  .0649     Anterior communicating artery  2 (3.2%)  3 (17.7%)  .0617     Middle cerebral artery  7 (11.1%)  0 (0.0%)  .3355     Basilar  9 (14.3%)  2 (11.8%)  1.0     Other  27 (42.9%)  5 (29.4%)  .4075    Circulation      .7258     Anterior  51 (79.7%)  15 (88.2%)       Posterior  13 (20.3%)  2 (11.8%)      Type      .7467     Proximal  51 (79.7%)  13 (76.5%)       Distal  13 (20.3%)  4 (23.5%)    Procedural factors  4-vessel angiogram  26 (40.6%)  6 (35.3%)  .6894    Intraprocedural heparin anticoagulation  64 (100.0%)  17 (100.0%)      Pharmacological neuroprotection  1 (1.6%)  0 (0.0%)  1.0    Total procedural time (min)  35.5 (26.2)  40.1 (25.7)  .5222    Total balloon inflation (min)  18.8 (11.7)  20.3 (11.9)  .6687    Balloon inflations  4.0 (2.5)  4.6 (2.2)  .4246    Average single inflation (min)  5.2 (2.8)  4.3 (1.7)  .0990    Maximum single inflation (min)  7.8 (4.7)  6.9 (2.6)  .3186    Total time down (min)  19.2 (16.2)  21.1 (15.1)  .6707    Maximum time down (min)  8.6 (5.2)  9.6 (6.9)  .5199  Outcome  Symptomatic stroke  3 (4.7%)  2 (11.8%)  .2808    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .3882    Modified Rankin scale score      .9502     0  41 (67.2%)  13 (76.5%)       1  13 (21.3%)  3 (17.7%)       2  4 (6.6%)  1 (5.9%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.6%)  0 (0.0%)       5  0 (0.0%)  0 (0.0%)       6  2 (3.3%)  0 (0.0%)      mRS 0-2  58 (95.1%)  17 (100.0%)  1.0  View Large Overall, SAH patients were found to have a significantly higher number and total volume of DWI abnormalities than non-SAH patients (4.0 vs 3.0, P = .0421 and 1.3 vs 0.3 cc, P = .0041; Table 5). However, while the number and total volume of DWI in the vascular territory distal to the aneurysm was not significantly different between the 2 groups, those with SAH were significantly more likely to have DWI abnormalities in vascular territories unrelated to the index aneurysm (81.5% vs 47.1%; P = .0235). TABLE 5. Comparison of Number and Volume of DWI Abnormality by SAH Status   SAH (n = 27)  No SAH (n = 19)a      Median (interquartile range)  Median (interquartile range)  P-value  Number of DWI  4.0 (2.0-9.0)  3.0 (1.0-4.0)  .0421  Total volume of DWI  1.3 (0.5-6.6)  0.3 (0.1-0.8)  .0041    SAH (n = 27)  No SAH (n = 19)a      Median (interquartile range)  Median (interquartile range)  P-value  Number of DWI  4.0 (2.0-9.0)  3.0 (1.0-4.0)  .0421  Total volume of DWI  1.3 (0.5-6.6)  0.3 (0.1-0.8)  .0041  aTotal Volume of DWI only available for 17 of the 19 no-SAH subjects. bWilcoxon rank sum test due to nonnormal data reported with medians. The means and standard deviations are as follows: for number of DWI, 7.0 (7.9) for SAH and 2.9 (2.0) for no SAH; for total volume, 7.5 (15.4) for SAH and 1.0 (1.8) for no SAH. The t-test has a P-value of .0168 for number of DWI and .039 for total volume. I suggest reporting the medians and Wilcoxon test from the table since the data are not normally distributed. View Large Among patients in the no-SAH group, DWI abnormalities were less common, antiplatelet use was more common. In addition, overall antiplatelet use prior to aneurysm treatment was associated with a significant decrease in incidence of DWI, but this effect was no longer significant on multivariate analysis. DWI Abnormalities and Outcomes Among all patients, those with a DWI abnormality were significantly less likely to have a good outcome (mRS 0-2) than patients without any DWI abnormality (95.6% vs 81.6%; P = .03). However, despite a higher overall rate of DWI in the SAH group, rates of symptomatic DWI were no different between the 2. Multivariate Analysis To assess which variables are independently associated with SAH or DWI, a multivariable logistic regression analysis was conducted on all covariates identified in baseline comparison, and a backward-stepwise approach was taken. The multivariable logistic regression identified 4-vessel angiogram (odds ratio [OR]: 82.2, confidence interval [CI] = [8.2, 821.1]), anterior communicating artery location (OR: 27.0, CI = [4.7, 154.3]), and DWI (OR: 15.8, CI = [3.9, 63.7]) as being independently associated with SAH. The multivariable logistic regression identified anterior communicating artery location (OR: 5.3, CI = [1.8, 15.1]) and, though not statistically significantly significant, mRS between 0 and 2 (OR: 0.24, CI = [0.1, 1.1]) as being independently associated with DWI. For these comparisons, an OR > 1 indicates a risk factor and OR < 1 indicates a protective factor. DISCUSSION Balloon Remodeling: Benefits and Drawbacks The technique of balloon-assisted coiling of intracranial aneurysms has been in use since 1999, with early literature on the technique demonstrating it to be effective in improving overall aneurysm occlusion rates.13 This technique has allowed for more effective coil embolization of anatomically difficult aneurysms, such as broad-neck aneurysms, as well as aneurysms in difficult locations, such as the middle cerebral artery.14,15 However, there are potential drawbacks to balloon use. Balloon inflation causes occlusion of anterograde flow so that the territory distal to the balloon inflation relies on indirect collateral supply. Structures supplied by perforators may be at higher risk of ischemia, as they lack robust collateral networks. In addition, the introduction of a balloon catheter, even if deflated, adds significant hardware to the intraluminal compartment and may incite thromboemboli.16 Although the early literature suggested that balloon-assisted coiling of cerebral aneurysms posited a higher risk of procedural complications,10 more recent literature has shown that balloon-assisted coiling is both safe and effective.17,18 In our own previous series, we have shown that use of the balloon in patients without SAH does not increase risk of procedural complications.11 However, there is some concern that use of the balloon in the setting of SAH may result in an increased incidence of complications, particularly ischemic events. Considerable work has been done to demonstrate that a consistent proinflammatory response exists following the rupture of an intracranial aneurysm,19,20,21 and that prothrombotic factors are elevated in this patient cohort. In a series of 681 patients with SAH, van Rooj et al10 showed that balloon use was significantly associated with thromboembolic complications. Santillan et al22 showed a trend toward higher rates of thromboembolic events in a group of SAH patients treated with balloon-assisted coiling as compared to unruptured patients, but the study was not powered to show a statistical significance. Balloon Remodeling and Ischemic Events Conventional wisdom endorses that repeated balloon inflations for aneurysm coil embolization in the setting of SAH may pose an undue risk of ischemic complications given the presumed systemic prothrombotic state of the critically ill SAH patient. However, studies to date have not been able to address this concern. What makes this dataset unique is the availability of the balloon inflation practice details (number of inflations, cumulative inflation time, etc.), postprocedure DWI imaging, and the fact that we have a control group of patients also treated with balloon remodeling, but in the unruptured setting (no SAH). In our series, we show a statistically significant increase in the overall number of DWI abnormalities in SAH patients with balloon remodeling compared to those without SAH treated with balloon remodeling. At first glance, these data might appear to support the notion that balloon use in the setting of SAH poses an undue risk of downstream emboli. However, a closer look reveals this not to be the case. There was no significant difference in the incidence of DWI abnormalities in the vascular territory distal to the treated aneurysm (and, hence, the site of balloon inflations). Furthermore, patients with aneurysms treated in the setting of SAH were much more commonly undergoing a complete cerebral angiogram. Together, these data provide evidence that these ischemic findings are unrelated to the use of the balloon, but perhaps are rather as a result of the complete diagnostic angiogram. While we cannot definitively conclude this from our dataset alone, we posit that these results are the byproduct of the widespread inflammatory and prothrombotic state that exists after SAH and that the catheter angiogram itself, as opposed to the devices used, represents the factor that places this patient cohort at risk for ischemic events.23 Of note, we expected antiplatelet use to be a protective factor against DWI events for the aforementioned reasons. While in our original analysis, patients on antiplatelets were significantly less likely to have a DWI (Table 2); this factor was not found to be significant on multivariate analysis. It may be that this association is present, but our study is not appropriately powered to detect such a difference. DWI Abnormalities and Outcome While most of the DWI abnormalities were silent events without clinical manifestation and the incidence of symptomatic DWI events (ie, those associated with a neurological deficit referable to a DWI abnormality seen on MRI) were the same between the SAH and no-SAH groups, a significant difference in outcomes was identified among patients with and without DWI abnormalities. Overall (SAH and no-SAH combined), patients with DWI abnormalities were less likely to have a good neurological outcome (mRS 0-2). This finding reinforces the idea that efforts aimed at reducing any DWI (silent or not) associated with aneurysm treatment are worthwhile in any patient population. Limitations Our paper has several limitations. First, this study was retrospective in nature. While the nature of the clinical practice between the SAH and no-SAH groups did not differ, the data sets for each groups were not captured prospectively. We do not have an a priori power analysis to demonstrate that our study is appropriately powered to detect the differences studied. Finally, we do not have MRI scans done prior to angiography, which means that we cannot exclude the possibility that these patients had pre-existing ischemic events as a result of the ictus as opposed to the intervention. Additionally, in retrospect, a comparison between the SAH group and a group of SAH patients treated without balloon assistance would be very valuable, but these data are not available to us. Additionally, due to the unique data parameters collected, we cannot easily find a historical institutional or literature cohort to use as a comparison. We make these limitations plain in this manuscript not to imply our findings to be hard truth but rather to demonstrate transparency in research. While our study is not perfect, we do have a unique data set that we believe is a positive addition to the literature and can prove useful in the decision-making process of the astute, informed neurovascular surgeon. CONCLUSION This study supports the use of balloon remodeling as a safe method of securing ruptured aneurysms in the SAH setting. Balloon use was not associated with a higher incidence of either silent or symptomatic ischemic events as identified on postprocedure MRI in the vascular territory distal to the aneurysm. Other factors, such as 4-vessel angiography or the SAH milieu itself, may be responsible for an overall increase in DWI abnormality seen in areas distant from the lesion. More concentrated study of these factors in the future could help elucidate the culprits responsible for the phenomena observed in the study of our patient cohort. Disclosures Dr Spiotta has the following conflicts of interest: Penumbra (consulting, honorarium, speaker bureau), Pulsar Vascular (consulting, honorarium, speaker bureau), Microvention (consulting, honorarium, speaker bureau, research), Stryker (consulting, honorarium, speaker bureau). Drs Turk, Turner, and Chaudry have the following conflicts of interest: Codman (consulting, honorarium, speaker bureau, research funding), Covidien (Consulting, Honorarium, Speaker Bureau), Penumbra (consulting, honorarium, speaker bureau, research grants), Microvention (consulting, honorarium, speaker bureau, research grants), Blockade (stock, consulting, honorarium, speaker bureau), Pulsar Vascular (stock, consulting, honorarium, speaker bureau, research), Medtronic (consulting, honorarium, speaker bureau). The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Zacharia BE, Hickman ZL, Grobelny BT et al.   Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin Am . 2010; 21( 2): 221- 233. Google Scholar CrossRef Search ADS   2. Miller BA, Turan N, Chau M, Pradilla G. Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage. Biomed Res Int . 2014; 2014: 384342. doi:10.1155/2014/384342. Google Scholar PubMed  3. Takizawa T, Tada T, Kitazawa K et al.   Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res . 2001; 23( 7): 724- 730. Google Scholar CrossRef Search ADS PubMed  4. Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost . 2005; 3( 10): 2185- 2192. Google Scholar CrossRef Search ADS PubMed  5. Prodan CI, Vincent AS, Kirkpatrick AC, Hoover SL, Dale GL. Higher levels of coated-platelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days. J Neurol Sci . 2013; 334( 1-2): 126- 129. Google Scholar CrossRef Search ADS PubMed  6. Frontera JA, Aledort L, Gordon E et al.   Early platelet activation, inflammation and acute brain injury after a subarachnoid hemorrhage: a pilot study. J Thromb Haemost . 2012; 10( 4): 711- 713. Google Scholar CrossRef Search ADS PubMed  7. Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol . 2002; 88( 3): 227- 249. Google Scholar CrossRef Search ADS PubMed  8. Santillan A, Gobin YP, Mazura JC et al.   Balloon-assisted coil embolization of intracranial aneurysms is not associated with increased periprocedural complications. J Neurointerv Surg . 2013; 5( suppl 3): iii56- iii61. Google Scholar CrossRef Search ADS PubMed  9. Shapiro M, Babb J, Becske T, Nelson PK. Safety and efficacy of adjunctive balloon remodeling during endovascular treatment of intracranial aneurysms: a literature review. AJNR Am J Neuroradiol . 2008; 29( 9): 1777- 1781. Google Scholar CrossRef Search ADS PubMed  10. van Rooij WJ, Sluzewski M, Beute GN, Nijssen PC. Procedural complications of coiling of ruptured intracranial aneurysms: incidence and risk factors in a consecutive series of 681 patients. AJNR Am J Neuroradiol . 2006; 27( 7): 1498- 1501. Google Scholar PubMed  11. Spiotta AM, Bhalla T, Hussain MS et al.   An analysis of inflation times during balloon-assisted aneurysm coil embolization and ischemic complications. Stroke . 2011; 42( 4): 1051- 1055. Google Scholar CrossRef Search ADS PubMed  12. Sims JR, Gharai LR, Schaefer PW et al.   ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology . 2009; 72( 24): 2104- 2110. Google Scholar CrossRef Search ADS PubMed  13. Lefkowitz MA, Gobin YP, Akiba Y et al.   Ballonn-assisted Guglielmi detachable coiling of wide-necked aneurysma: part II—clinical results. Neurosurgery . 1999; 45( 3): 531- 537; discussion 537-538. Google Scholar CrossRef Search ADS PubMed  14. Chen PR. Balloon-assisted coil embolization of small intracranial aneurysms. Neurosurg Focus . 2014; 37( 1 suppl): 1. Google Scholar CrossRef Search ADS PubMed  15. Kim BM, Kim DI, Park SI, Kim DJ, Suh SH, Won YS. Coil embolization of unruptured middle cerebral artery aneurysms. Neurosurgery . 2011; 68( 2): 346- 353; discussion 353-344. Google Scholar CrossRef Search ADS PubMed  16. Takigawa T, Suzuki K, Sugiura Y et al.   Thromboembolic events associated with single balloon-, double balloon-, and stent-assisted coil embolization of asymptomatic unruptured cerebral aneurysms: evaluation with diffusion-weighted MR imaging. Neuroradiology . 2014; 56( 12): 1079- 1086. Google Scholar CrossRef Search ADS PubMed  17. Pierot L, Cognard C, Spelle L, Moret J. Safety and efficacy of balloon remodeling technique during endovascular treatment of intracranial aneurysms: critical review of the literature. AJNR Am J Neuroradiol . 2012; 33( 1): 12- 15. Google Scholar CrossRef Search ADS PubMed  18. Ramakrishnan V, Quadri S, Sodhi A, Cortez V, Taqi M. E-064 safety and efficacy of balloon-assisted coiling of intracranial aneurysms: a single-center study. J Neurointerv Surg . 2014; 6( suppl 1): A68- A69. Google Scholar CrossRef Search ADS   19. Larsen CC, Hansen-Schwartz J, Nielsen JD, Astrup J. Blood coagulation and fibrinolysis after experimental subarachnoid hemorrhage. Acta Neurochir (Wien) . 2010; 152( 9): 1577- 1581; discussion 1581. Google Scholar CrossRef Search ADS PubMed  20. Sehba FA, Mostafa G, Friedrich V Jr, Bederson JB. Acute microvascular platelet aggregation after subarachnoid hemorrhage. J Neurosurg . 2005; 102( 6): 1094- 1100. Google Scholar CrossRef Search ADS PubMed  21. Tang QF, Lu SQ, Zhao YM, Qian JX. The changes of von willebrand factor/a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 balance in aneurysmal subarachnoid hemorrhage. Int J Clin Exp Med . 2015; 8( 1): 1342- 1348. Google Scholar PubMed  22. Sato M, Nakai Y, Tsurushima H, Shiigai M, Masumoto T, Matsumura A. Risk factors of ischemic lesions related to cerebral angiography and neuro-interventional procedures. Neurol Med Chir (Tokyo) . 2013; 53( 6): 381- 387. Google Scholar CrossRef Search ADS PubMed  23. Santillan A, Gobin YP, Greenberg ED et al.   Intraprocedural aneurysmal rupture during coil embolization of brain aneurysms: role of balloon-assisted coiling. AJNR Am J Neuroradiol . 2012; 33( 10): 2017- 2021. Google Scholar CrossRef Search ADS PubMed  Acknowledgment Alyssa Pierce assisted with the editing and revision of this manuscript. Copyright © 2017 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

A Comparison of Diffusion-Weighted Imaging Abnormalities Following Balloon Remodeling for Aneurysm Coil Embolization in the Ruptured vs Unruptured Setting

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Copyright © 2017 by the Congress of Neurological Surgeons
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0148-396X
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1524-4040
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10.1093/neuros/nyx240
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Abstract

Abstract BACKGROUND The prothrombotic milieu seen in subarachnoid hemorrhage (SAH) poses a unique challenge to neurovascular surgeons with regard to device use and microcatheter practice. OBJECTIVE To determine how demographic factors and balloon practices impact diffusion-weighted imaging (DWI) abnormalities and outcomes in patients with SAH compared to those without (non-SAH). METHODS We retrospectively analyzed 77 patients with SAH treated by balloon-assisted coiling in a single institution compared with 81 consecutive patients with unruptured aneurysms treated by balloon-assisted coiling at the same institution. Data were collected with regard to demographic factors, procedural and anatomic considerations, and DWI abnormalities on postprocedural magnetic resonance imaging. RESULTS SAH patients were significantly more likely to have DWI abnormality (75% vs 21%, P < .0001) and had a higher number and volume of DWI (4.0 vs 3.0, P = .0421 and 1.3 vs 0.3 cc, P = .0041) despite similar balloon practices. SAH patients were not more likely to have DWI abnormality in vascular territory distal to the treated aneurysm but had a higher likelihood of DWI in a vascular territory unrelated to the aneurysm (81.5% vs 47.1%, P = .0235). Patients without DWI abnormality were significantly more likely to have a good outcome as defined by modified Rankin Score 0 to 2 (95.6% vs 81.6%, P = .0328). Patients with DWI abnormality more often underwent 4-vessel angiography (70.5% vs 48.0%, P = .0174), but this was not found to be significant on multivariate analysis. CONCLUSION Balloon-assisted coiling does not result in increased incidence of downstream ischemic events in SAH patients compared to non-SAH patients and is safe in this cohort of patients. Other factors, such as 4-vessel angiography of the SAH milieu itself, may predispose patients to a higher rate of ischemic events. Subarachnoid hemorrhage, Diffusion-weighted imaging ABBREVIATIONS ABBREVIATIONS CI confidence interval DWI diffusion-weighted imaging MRI magnetic resonance imaging mRS modified Rankin Score OR odds ratio SAH subarachnoid hemorrhage Subarachnoid hemorrhage (SAH) is a morbid disease affecting as many as 30 000 patients per year in the United States, with ruptured intracranial aneurysm being responsible for approximately 80% of these cases.1 Evidence exists to support the notion that aneurysmal SAH incites a systemic proinflammatory state. There is a volume of evidence that proinflammatory markers are seen in the blood and cerebrospinal fluid following SAH.2,3 Additionally, it is thought that this proinflammatory state also induces a prothrombotic state immediately following aneurysmal SAH,4,5,6 and that prothrombotic markers are significantly higher in poor-grade SAH patients.7 Endovascular coiling is rapidly becoming standard of care for the majority of patients with intracranial aneurysms indicated for treatment, and the technique of balloon-assisted coiling has become commonplace in cases of geometrically difficult aneurysms not amenable to standard embolization techniques. In general, the recent literature to date supports balloon-assisted coiling as safe and effective,8,9 although the balloon technique has been associated with increased complications in an isolated series of SAH patients.10 We present a group of patients with and without SAH who underwent balloon-assisted coil embolization, analyzing number, volume, and location of diffusion abnormalities on magnetic resonance imaging (MRI) between the 2 groups with regard to balloon inflation practice and demographic factors. METHODS A retrospective chart review was undertaken of 77 consecutive patients with aneurysmal SAH in which the index aneurysm was treated by balloon remodeling at a single institution, a metropolitan tertiary care facility. Standard institutional practice for SAH patients was followed, including comanagement by neurosurgery and neurocritical care and aneurysm treatment within 24 h via a “coil-first” policy. All patients underwent a 4-vessel angiogram per protocol. This study was approved by the institutional review board. A group of 81 consecutive patients (previously reported)11 with unruptured aneurysms treated by balloon remodeling over the same time period at the same institution serve as an internal control group. Demographics Data were collected by the senior author (AMS) with respect to age, gender, history of hypertension, history of diabetes, history of tobacco usage, previous stroke, and antiplatelet (ie, use of aspirin, clopidogrel, or both) use in both groups. Procedural and Anatomic Considerations All patients underwent digital subtraction angiography under general endotracheal anesthesia in the neuroangiography suite. Blood pressure was maintained with a goal systolic blood pressure <140 mm Hg and mean arterial pressure >65 mm Hg, and was not pharmacologically augmented during balloon inflations. Patients were classified as having a 4-vessel angiogram if they underwent a full diagnostic cerebral angiogram prior to their intervention, as opposed to a case in which only the vessel of interest was selected. With respect to balloon inflation practice, total procedural time, cumulative balloon inflation time, number of balloon inflations, average and maximum single inflation times, and total and maximum times deflated were recorded for each patient in minutes and seconds. Intraprocedural heparin was administered prior to insertion of guide catheter in all patients in both groups. In general, the standard guide catheters used at the treating institution were either a 6-French Envoy or a 0 to 70 Neuron catheter. The balloon was either a Hyperglide or Hyperform. An SL-10 catheter was preferred as an access catheter. The number, size, and type of coil was variable based on the individual morphology of each aneurysm. If individual patient circumstance demanded, other materials could be used. Imaging All patients in both the SAH and the no-SAH group were protocolled to undergo postprocedural MRI within 24 h of procedure, but owing to logistical factors, 44 patients in the SAH group were not able to undergo the scan within the allotted window. These images were reviewed by a single reviewer for location and volume of abnormal diffusion-weighted imaging (DWI) signal using the technique as described by Sims et al.12 The reviewer was blinded with regard to treatment for each imaging study. DWI abnormalities were categorized as either being in a vascular territory distal to the aneurysm or in a vascular territory unrelated to the aneurysm (“other”). Radiographic review was performed by a single, independent reviewer who was blinded to treatment. Outcome DWI lesions were classified as symptomatic if they were associated with a neurological deficit referable to the anatomic area of the lesion, or as asymptomatic. A modified Rankin Score (mRS) was assessed at most recent follow-up or at 90 d (whichever was later), and patients were stratified according to mRS 0 to 2 or mRS 3 to 6. Statistical Analysis Statistical analyses were performed using SAS Version 9.3 (SAS Institute, Cary, North Carolina). A population of 158 subjects was analyzed using descriptive statistics to characterize injury type, balloon procedures, and procedural complications and outcomes. Differences between groups were tested using a chi-square test for categorical measures or Fisher's exact test for categorical measures with expected cell sizes under 5. Differences between groups were assessed using the paired t-test or analysis of variance for normally distributed continuous measures. Balloon practices and number and volume of DWI were compared across 2 groups using the Wilcoxon signed rank test and across 3 groups using the Kruskal–Wallis test due to nonnormally distributed data. The correlation between total inflation time, number of inflations, maximum single inflation, mean inflation, and inflation downtime with volume and number of DWI was assessed using Spearman rank correlation. Finally, a multivariate analysis was performed, as described in the Results section. All tests were assessed at a significance level of 0.05. RESULTS A total of 158 patients were treated with balloon remodeling and are included in this study. Seventy-seven patients (57% female, aged 54 ± 13 yr) underwent coil embolization of a ruptured cerebral aneurysm with balloon remodeling (SAH group). Eighty-one patients (88% female; aged 57 ± 12 yr) underwent coil embolization of an unruptured cerebral aneurysm with balloon remodeling in the elective setting (no-SAH group). Table 1 shows the comparison data between the SAH and no-SAH groups. TABLE 1. Population Comparison Between Subarachnoid and Nonsubarachnoid Subjects (n = 158)   n  SAH (n = 77)  No SAH (n = 81)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Gender  158      <.0001   Female    44 (57.1%)  72 (88.9%)     Male    33 (42.9%)  9 (11.1%)    Age (years)  158  54.6 (13.8)  57.6 (12.4)  .1651  Hypertension  158  33 (42.9%)  41 (50.6%)  .3285  Diabetes  158  8 (10.4%)  10 (12.4%)  .6989  Tobacco  158      .0301   Current    44 (57.1%)  33 (40.7%)     Remote    9 (11.7%)  22 (27.2%)     None    24 (31.2%)  26 (32.1%)    Antiplatelets  158  27 (35.1%)  51 (63.0%)  .0005  Previous stroke  158  1 (1.3%)  15 (18.5%)  .0003  4-vessel angiogram  158  74 (96.1%)  32 (39.5%)  <.0001  Intraprocedural heparin anticoagulation  158  77 (100.0%)  81 (100.0%)  1.0  Pharmacological neuroprotection  158  0 (0.0%)  1 (1.2%)  1.0  Aneurysm location  157         Internal carotid artery    7 (9.1%)  11 (13.8%)  .4549   Posterior communicating artery    11 (14.3%)  14 (17.5%)  .5821   Anterior communicating artery    33 (42.9%)  5 (6.3%)  <.0001   Middle cerebral artery    3 (3.9%)  7 (8.8%)  .3285   Basilar    7 (9.1%)  11 (13.8%)  .4549   Othera    16 (20.8%)  32 (40.0%)  .0090  Procedure times           Total procedural time (min)  120  28.7 (36.5)  36.6 (26.0)  .1961   Total balloon inflation (min)  120  12.3 (14.3)  19.2 (11.7)  .0047   Balloon inflations  123  3.3 (2.4)  4.2 (2.5)  .0689   Average single inflation (min)  120  4.8 (6.6)  5.0 (2.6)  .8459   Maximum single inflation (min)  120  6.5 (8.3)  7.6 (4.3)  .3700   Total time down (min)b  99  21.8 (30.5)  19.7 (15.8)  .6967   Maximum time down (min)b  99  14.3 (20.4)  8.8 (5.6)  .1233  DWI in vascular territory distal to aneurysmc    18 (66.7%)  15 (88.2%)  .1585  DWI in other territoryc    22 (81.5%)  8 (47.1%)  .0235  Overall DWI rate  117  27 (75.0%)  17 (21.0%)  <.0001    n  SAH (n = 77)  No SAH (n = 81)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Gender  158      <.0001   Female    44 (57.1%)  72 (88.9%)     Male    33 (42.9%)  9 (11.1%)    Age (years)  158  54.6 (13.8)  57.6 (12.4)  .1651  Hypertension  158  33 (42.9%)  41 (50.6%)  .3285  Diabetes  158  8 (10.4%)  10 (12.4%)  .6989  Tobacco  158      .0301   Current    44 (57.1%)  33 (40.7%)     Remote    9 (11.7%)  22 (27.2%)     None    24 (31.2%)  26 (32.1%)    Antiplatelets  158  27 (35.1%)  51 (63.0%)  .0005  Previous stroke  158  1 (1.3%)  15 (18.5%)  .0003  4-vessel angiogram  158  74 (96.1%)  32 (39.5%)  <.0001  Intraprocedural heparin anticoagulation  158  77 (100.0%)  81 (100.0%)  1.0  Pharmacological neuroprotection  158  0 (0.0%)  1 (1.2%)  1.0  Aneurysm location  157         Internal carotid artery    7 (9.1%)  11 (13.8%)  .4549   Posterior communicating artery    11 (14.3%)  14 (17.5%)  .5821   Anterior communicating artery    33 (42.9%)  5 (6.3%)  <.0001   Middle cerebral artery    3 (3.9%)  7 (8.8%)  .3285   Basilar    7 (9.1%)  11 (13.8%)  .4549   Othera    16 (20.8%)  32 (40.0%)  .0090  Procedure times           Total procedural time (min)  120  28.7 (36.5)  36.6 (26.0)  .1961   Total balloon inflation (min)  120  12.3 (14.3)  19.2 (11.7)  .0047   Balloon inflations  123  3.3 (2.4)  4.2 (2.5)  .0689   Average single inflation (min)  120  4.8 (6.6)  5.0 (2.6)  .8459   Maximum single inflation (min)  120  6.5 (8.3)  7.6 (4.3)  .3700   Total time down (min)b  99  21.8 (30.5)  19.7 (15.8)  .6967   Maximum time down (min)b  99  14.3 (20.4)  8.8 (5.6)  .1233  DWI in vascular territory distal to aneurysmc    18 (66.7%)  15 (88.2%)  .1585  DWI in other territoryc    22 (81.5%)  8 (47.1%)  .0235  Overall DWI rate  117  27 (75.0%)  17 (21.0%)  <.0001  SAH, subarachnoid hemorrhage; DWI, diffusion-weighted imaging abnormality. aOther includes A1/A2, ophthalmic, posterior inferior cerebellar artery (PICA); superior cerebellar artery (SCA); superior hypophyseal artery (SHA); vertebral, and pericallosal. bSixteen subjects had a single-balloon inflation. cNineteen subjects had a DWI in both the vascular and other territory. They are shown in both groups. View Large Patient Risk Factors: Comorbidities No significant differences were identified between the 2 groups with regard to age, history of hypertension, or history of diabetes. SAH patients were more likely to be female (42.9% vs 11.1%; P < .0001) and have a history of tobacco use (57% vs 40%; P = .03) compared to those with unruptured aneurysms. Significantly more patients in the no-SAH group were on antiplatelet agents than the SAH patients (63% vs 35%; P = .0005). Procedural Factors and Balloon Inflation All patients in both groups underwent intraprocedural heparin anticoagulation with an identical initial bolus and activated clogging time goal, which was 2.5 times the baseline partial thromboplastin time. Heparin was administered prior to guide catheter placement. SAH patients were more likely to undergo a complete diagnostic cerebral angiogram at the time of treatment of the index aneurysm than no-SAH patients; however, total procedural times did not significantly differ between the 2 groups. Total number of balloon inflations, the average single inflation time, maximum single inflation time, total time deflated, and minimum time deflated did not differ between the 2 groups. However, SAH patients were treated with a significantly lower cumulative balloon inflation time compared to the no-SAH patients (12.3 ± 14.3 vs 19.2 ± 11.7 min; P = .0047). DWI Abnormalities SAH patients were more likely to have a DWI abnormality of any type, in any territory, on postprocedural MRI compared to no-SAH patients (75% vs 21%; P < .0001). Grouping all patients (Table 2) demonstrates that patients with DWI were more likely to be male, have undergone a 4-vessel angiogram, and been treated for an anterior communicating artery aneurysm. Among SAH patients alone, no differences were encountered on either demographic, procedural, or anatomic factors among patients with DWI abnormalities compared to those in whom no DWI were found on postprocedure MRI (Table 3). Among no-SAH patients, history of diabetes was significantly higher in those with DWI abnormality as compared to those without (Table 4). TABLE 2. Demographic Comparison between Cohorts with and without DWI Abnormality     No DWI (n = 73)  DWI (n = 44)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0187     Female  63 (86.3%)  30 (68.2%)       Male  10 (13.7%)  14 (31.8%)      Age (years)  55.9 (12.6)  58.3 (13.2)  .3369    Hypertension  34 (46.6%)  22 (50.0%)  .7194    Diabetes  6 (8.2%)  7 (15.9%)  .2325    Tobacco      .2561     Current  30 (41.1%)  25 (56.8%)       Remote  18 (24.7%)  8 (18.2%)       None  25 (34.3%)  11 (25.0%)      Antiplatelets  46 (63.0%)  19 (43.2%)  .0365    Previous stroke  12 (16.4%)  3 (6.8%)  .1617  Anatomic factors  Aneurysm location           Internal carotid artery  10 (13.9%)  3 (6.8%)  .3648     Posterior communicating artery  10 (13.9%)  8 (18.2%)  .6011     Anterior communicating artery  8 (11.1%)  17 (38.6%)  .0008     Middle cerebral artery  7 (9.7%)  0 (0.0%)  .0433     Basilar  9 (12.5%)  4 (9.1%)  .7638     Other  28 (38.9%)  12 (27.8%)  .2015    Circulation           Anterior  60 (82.2%)  36 (81.8%)  .9593     Posterior  13 (17.8%)  8 (18.2%)      Type      .7227     Proximal  60 (82.2%)  35 (79.6%)       Distal  13 (17.8%)  9 (20.5%)    Procedural factors  4-vessel angiogram  35 (48.0%)  31 (70.5%)  .0174    Intraprocedural heparin Anticoagulation  73 (100.0%)  44 (100.0%)  1.0    Pharmacological neuroprotection  1 (1.4%)  0 (0.0%)  1.0    Total procedural time (min)  35.3 (28.5)  29.2 (29.3)  .3133    Total balloon inflation (min)  18.8 (14.3)  14.3 (11.4)  .1096    Balloon inflations  3.8 (2.5)  3.8 (2.5)  .8784    Average single inflation (min)  5.7 (5.4)  4.2 (3.1)  .1061    Maximum single inflation (min)  8.3 (7.6)  6.2 (4.1)  .0757    Total time down (min)  19.3 (17.3)  19.1 (23.4)  .9588    Maximum time down (min)  8.5 (9.7)  7.9 (11.9)  .7815  Outcome  Symptomatic stroke  4 (5.8%)  8 (18.2%)  .0578    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .6249    Modified Rankin scale score (mRS)      .1843     0  44 (64.7%)  20 (52.6%)       1  14 (20.6%)  6 (15.8%)       2  7 (10.3%)  5 (13.2%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.5%)  3 (7.9%)       5  0 (0.0%)  0 (0.0%)       6  2 (2.9%)  4 (10.5%)      mRS 0-2  65 (95.6%)  31 (81.6%)  .0328      No DWI (n = 73)  DWI (n = 44)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0187     Female  63 (86.3%)  30 (68.2%)       Male  10 (13.7%)  14 (31.8%)      Age (years)  55.9 (12.6)  58.3 (13.2)  .3369    Hypertension  34 (46.6%)  22 (50.0%)  .7194    Diabetes  6 (8.2%)  7 (15.9%)  .2325    Tobacco      .2561     Current  30 (41.1%)  25 (56.8%)       Remote  18 (24.7%)  8 (18.2%)       None  25 (34.3%)  11 (25.0%)      Antiplatelets  46 (63.0%)  19 (43.2%)  .0365    Previous stroke  12 (16.4%)  3 (6.8%)  .1617  Anatomic factors  Aneurysm location           Internal carotid artery  10 (13.9%)  3 (6.8%)  .3648     Posterior communicating artery  10 (13.9%)  8 (18.2%)  .6011     Anterior communicating artery  8 (11.1%)  17 (38.6%)  .0008     Middle cerebral artery  7 (9.7%)  0 (0.0%)  .0433     Basilar  9 (12.5%)  4 (9.1%)  .7638     Other  28 (38.9%)  12 (27.8%)  .2015    Circulation           Anterior  60 (82.2%)  36 (81.8%)  .9593     Posterior  13 (17.8%)  8 (18.2%)      Type      .7227     Proximal  60 (82.2%)  35 (79.6%)       Distal  13 (17.8%)  9 (20.5%)    Procedural factors  4-vessel angiogram  35 (48.0%)  31 (70.5%)  .0174    Intraprocedural heparin Anticoagulation  73 (100.0%)  44 (100.0%)  1.0    Pharmacological neuroprotection  1 (1.4%)  0 (0.0%)  1.0    Total procedural time (min)  35.3 (28.5)  29.2 (29.3)  .3133    Total balloon inflation (min)  18.8 (14.3)  14.3 (11.4)  .1096    Balloon inflations  3.8 (2.5)  3.8 (2.5)  .8784    Average single inflation (min)  5.7 (5.4)  4.2 (3.1)  .1061    Maximum single inflation (min)  8.3 (7.6)  6.2 (4.1)  .0757    Total time down (min)  19.3 (17.3)  19.1 (23.4)  .9588    Maximum time down (min)  8.5 (9.7)  7.9 (11.9)  .7815  Outcome  Symptomatic stroke  4 (5.8%)  8 (18.2%)  .0578    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .6249    Modified Rankin scale score (mRS)      .1843     0  44 (64.7%)  20 (52.6%)       1  14 (20.6%)  6 (15.8%)       2  7 (10.3%)  5 (13.2%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.5%)  3 (7.9%)       5  0 (0.0%)  0 (0.0%)       6  2 (2.9%)  4 (10.5%)      mRS 0-2  65 (95.6%)  31 (81.6%)  .0328  View Large TABLE 3. Demographic Comparison of SAH Subjects With and Without DWI Abnormality     No DWI (n = 9)  DWI (n = 27)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .4427     Female  4 (44.4%)  17 (63.0%)       Male  5 (55.6%)  10 (37.0%)      Age (years)  53.7 (14.3)  55.7 (13.9)  .7126    Hypertension  3 (33.3%)  12 (44.4%)  .7050    Diabetes  2 (22.2%)  1 (3.7%)  .1479    Tobacco      .8573     Current  5 (55.6%)  17 (63.0%)       Remote  1 (11.1%)  3 (11.1%)       None  3 (33.3%)  7 (25.9%)      Antiplatelets  4 (44.4%)  10 (37.0%)  .7115    Previous stroke  0 (0.0%)  0 (0.0%)    Anatomic factors  Aneurysm location           Internal carotid artery  0 (0.0%)  2 (7.4%)  1.0     Posterior communicating artery  2 (22.2%)  2 (7.4%)  .2552     Anterior communicating artery  6 (66.7%)  14 (51.9%)  .7003     Middle cerebral artery  0 (0.0%)  0 (0.0%)       Basilar  0 (0.0%)  2 (7.4%)  1.0     Other  1 (11.1%)  7 (25.9%)  .6478    Circulation      .3026     Anterior  9 (100.0%)  21 (77.8%)       Posterior  0 (0.0%)  6 (22.2%)      Type      .3017     Proximal  9 (100.0%)  22 (81.5%)       Distal  0 (0.0%)  5 (18.5%)    Procedural factors  4-vessel angiogram  9 (100.0%)  25 (92.6%)  1.0    Intraprocedural Heparin Anticoagulation  9 (100.0%)  27 (100.0%)      Pharmacological neuroprotection  0 (0.0%)  0 (0.0%)      Total procedural time (min)  33.9 (45.2)  19.9 (29.7)  .3581    Total balloon inflation (min)  18.1 (29.1)  9.2 (8.3)  .4542    Balloon inflations  2.3 (1.0)  3.1 (2.6)  .2696    Average single inflation (min)  8.8 (14.6)  4.2 (3.9)  .4414    Maximum single inflation (min)  12.0 (19.2)  5.6 (5.0)  .4113    Total time down (min)  20.6 (26.6)  16.3 (31.9)  .7846    Maximum time down (min)  19.4 (24.9)  10.8 (18.1)  .4134  Outcome  Symptomatic stroke  1 (20.0%)  6 (22.2%)  1.0    NIHSS (median [IQR])  0.5 (0-1)  0 (0-1)  .7489    Modified Rankin scale score (mRS)      .5704     0  3 (42.9%)  7 (33.3%)       1  1 (14.3%)  3 (14.3%)       2  3 (42.9%)  4 (19.1%)       3  0 (0.0%)  0 (0.0%)       4  0 (0.0%)  3 (14.3%)       5  0 (0.0%)  0 (0.0%)       6  0 (0.0%)  4 (19.1%)      mRS 0-2  7 (100.0%)  14 (66.7%)  .1414      No DWI (n = 9)  DWI (n = 27)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .4427     Female  4 (44.4%)  17 (63.0%)       Male  5 (55.6%)  10 (37.0%)      Age (years)  53.7 (14.3)  55.7 (13.9)  .7126    Hypertension  3 (33.3%)  12 (44.4%)  .7050    Diabetes  2 (22.2%)  1 (3.7%)  .1479    Tobacco      .8573     Current  5 (55.6%)  17 (63.0%)       Remote  1 (11.1%)  3 (11.1%)       None  3 (33.3%)  7 (25.9%)      Antiplatelets  4 (44.4%)  10 (37.0%)  .7115    Previous stroke  0 (0.0%)  0 (0.0%)    Anatomic factors  Aneurysm location           Internal carotid artery  0 (0.0%)  2 (7.4%)  1.0     Posterior communicating artery  2 (22.2%)  2 (7.4%)  .2552     Anterior communicating artery  6 (66.7%)  14 (51.9%)  .7003     Middle cerebral artery  0 (0.0%)  0 (0.0%)       Basilar  0 (0.0%)  2 (7.4%)  1.0     Other  1 (11.1%)  7 (25.9%)  .6478    Circulation      .3026     Anterior  9 (100.0%)  21 (77.8%)       Posterior  0 (0.0%)  6 (22.2%)      Type      .3017     Proximal  9 (100.0%)  22 (81.5%)       Distal  0 (0.0%)  5 (18.5%)    Procedural factors  4-vessel angiogram  9 (100.0%)  25 (92.6%)  1.0    Intraprocedural Heparin Anticoagulation  9 (100.0%)  27 (100.0%)      Pharmacological neuroprotection  0 (0.0%)  0 (0.0%)      Total procedural time (min)  33.9 (45.2)  19.9 (29.7)  .3581    Total balloon inflation (min)  18.1 (29.1)  9.2 (8.3)  .4542    Balloon inflations  2.3 (1.0)  3.1 (2.6)  .2696    Average single inflation (min)  8.8 (14.6)  4.2 (3.9)  .4414    Maximum single inflation (min)  12.0 (19.2)  5.6 (5.0)  .4113    Total time down (min)  20.6 (26.6)  16.3 (31.9)  .7846    Maximum time down (min)  19.4 (24.9)  10.8 (18.1)  .4134  Outcome  Symptomatic stroke  1 (20.0%)  6 (22.2%)  1.0    NIHSS (median [IQR])  0.5 (0-1)  0 (0-1)  .7489    Modified Rankin scale score (mRS)      .5704     0  3 (42.9%)  7 (33.3%)       1  1 (14.3%)  3 (14.3%)       2  3 (42.9%)  4 (19.1%)       3  0 (0.0%)  0 (0.0%)       4  0 (0.0%)  3 (14.3%)       5  0 (0.0%)  0 (0.0%)       6  0 (0.0%)  4 (19.1%)      mRS 0-2  7 (100.0%)  14 (66.7%)  .1414  View Large TABLE 4. Demographic Comparison of Non-SAH Subjects With and Without DWI Abnormality     No DWI (n = 64)  DWI (n = 17)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0868     Female  59 (92.2%)  13 (76.5%)       Male  5 (7.8%)  4 (23.5%)      Age (years)  56.3 (12.4)  62.4 (11.3)  .0656    Hypertension  31 (48.4%)  10 (58.8%)  .4464    Diabetes  4 (6.3%)  6 (35.3%)  .0046    Tobacco      .7821     Current  25 (39.1%)  8 (47.1%)       Remote  17 (26.6%)  5 (29.4%)       None  22 (34.4%)  4 (23.5%)      Antiplatelets  42 (65.6%)  9 (52.9%)  .3357    Previous stroke  12 (18.8%)  3 (17.7%)  1.0  Anatomic factors  Aneurysm location           Internal carotid artery  10 (15.9%)  1 (5.9%)  .4414     Posterior communicating artery  8 (12.7%)  6 (35.3%)  .0649     Anterior communicating artery  2 (3.2%)  3 (17.7%)  .0617     Middle cerebral artery  7 (11.1%)  0 (0.0%)  .3355     Basilar  9 (14.3%)  2 (11.8%)  1.0     Other  27 (42.9%)  5 (29.4%)  .4075    Circulation      .7258     Anterior  51 (79.7%)  15 (88.2%)       Posterior  13 (20.3%)  2 (11.8%)      Type      .7467     Proximal  51 (79.7%)  13 (76.5%)       Distal  13 (20.3%)  4 (23.5%)    Procedural factors  4-vessel angiogram  26 (40.6%)  6 (35.3%)  .6894    Intraprocedural heparin anticoagulation  64 (100.0%)  17 (100.0%)      Pharmacological neuroprotection  1 (1.6%)  0 (0.0%)  1.0    Total procedural time (min)  35.5 (26.2)  40.1 (25.7)  .5222    Total balloon inflation (min)  18.8 (11.7)  20.3 (11.9)  .6687    Balloon inflations  4.0 (2.5)  4.6 (2.2)  .4246    Average single inflation (min)  5.2 (2.8)  4.3 (1.7)  .0990    Maximum single inflation (min)  7.8 (4.7)  6.9 (2.6)  .3186    Total time down (min)  19.2 (16.2)  21.1 (15.1)  .6707    Maximum time down (min)  8.6 (5.2)  9.6 (6.9)  .5199  Outcome  Symptomatic stroke  3 (4.7%)  2 (11.8%)  .2808    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .3882    Modified Rankin scale score      .9502     0  41 (67.2%)  13 (76.5%)       1  13 (21.3%)  3 (17.7%)       2  4 (6.6%)  1 (5.9%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.6%)  0 (0.0%)       5  0 (0.0%)  0 (0.0%)       6  2 (3.3%)  0 (0.0%)      mRS 0-2  58 (95.1%)  17 (100.0%)  1.0      No DWI (n = 64)  DWI (n = 17)        n (%) or mean (st. dev.)  n (%) or mean (st. dev.)  P-value  Demographics  Gender      .0868     Female  59 (92.2%)  13 (76.5%)       Male  5 (7.8%)  4 (23.5%)      Age (years)  56.3 (12.4)  62.4 (11.3)  .0656    Hypertension  31 (48.4%)  10 (58.8%)  .4464    Diabetes  4 (6.3%)  6 (35.3%)  .0046    Tobacco      .7821     Current  25 (39.1%)  8 (47.1%)       Remote  17 (26.6%)  5 (29.4%)       None  22 (34.4%)  4 (23.5%)      Antiplatelets  42 (65.6%)  9 (52.9%)  .3357    Previous stroke  12 (18.8%)  3 (17.7%)  1.0  Anatomic factors  Aneurysm location           Internal carotid artery  10 (15.9%)  1 (5.9%)  .4414     Posterior communicating artery  8 (12.7%)  6 (35.3%)  .0649     Anterior communicating artery  2 (3.2%)  3 (17.7%)  .0617     Middle cerebral artery  7 (11.1%)  0 (0.0%)  .3355     Basilar  9 (14.3%)  2 (11.8%)  1.0     Other  27 (42.9%)  5 (29.4%)  .4075    Circulation      .7258     Anterior  51 (79.7%)  15 (88.2%)       Posterior  13 (20.3%)  2 (11.8%)      Type      .7467     Proximal  51 (79.7%)  13 (76.5%)       Distal  13 (20.3%)  4 (23.5%)    Procedural factors  4-vessel angiogram  26 (40.6%)  6 (35.3%)  .6894    Intraprocedural heparin anticoagulation  64 (100.0%)  17 (100.0%)      Pharmacological neuroprotection  1 (1.6%)  0 (0.0%)  1.0    Total procedural time (min)  35.5 (26.2)  40.1 (25.7)  .5222    Total balloon inflation (min)  18.8 (11.7)  20.3 (11.9)  .6687    Balloon inflations  4.0 (2.5)  4.6 (2.2)  .4246    Average single inflation (min)  5.2 (2.8)  4.3 (1.7)  .0990    Maximum single inflation (min)  7.8 (4.7)  6.9 (2.6)  .3186    Total time down (min)  19.2 (16.2)  21.1 (15.1)  .6707    Maximum time down (min)  8.6 (5.2)  9.6 (6.9)  .5199  Outcome  Symptomatic stroke  3 (4.7%)  2 (11.8%)  .2808    NIHSS (median [IQR])  0 (0-0)  0 (0-0)  .3882    Modified Rankin scale score      .9502     0  41 (67.2%)  13 (76.5%)       1  13 (21.3%)  3 (17.7%)       2  4 (6.6%)  1 (5.9%)       3  0 (0.0%)  0 (0.0%)       4  1 (1.6%)  0 (0.0%)       5  0 (0.0%)  0 (0.0%)       6  2 (3.3%)  0 (0.0%)      mRS 0-2  58 (95.1%)  17 (100.0%)  1.0  View Large Overall, SAH patients were found to have a significantly higher number and total volume of DWI abnormalities than non-SAH patients (4.0 vs 3.0, P = .0421 and 1.3 vs 0.3 cc, P = .0041; Table 5). However, while the number and total volume of DWI in the vascular territory distal to the aneurysm was not significantly different between the 2 groups, those with SAH were significantly more likely to have DWI abnormalities in vascular territories unrelated to the index aneurysm (81.5% vs 47.1%; P = .0235). TABLE 5. Comparison of Number and Volume of DWI Abnormality by SAH Status   SAH (n = 27)  No SAH (n = 19)a      Median (interquartile range)  Median (interquartile range)  P-value  Number of DWI  4.0 (2.0-9.0)  3.0 (1.0-4.0)  .0421  Total volume of DWI  1.3 (0.5-6.6)  0.3 (0.1-0.8)  .0041    SAH (n = 27)  No SAH (n = 19)a      Median (interquartile range)  Median (interquartile range)  P-value  Number of DWI  4.0 (2.0-9.0)  3.0 (1.0-4.0)  .0421  Total volume of DWI  1.3 (0.5-6.6)  0.3 (0.1-0.8)  .0041  aTotal Volume of DWI only available for 17 of the 19 no-SAH subjects. bWilcoxon rank sum test due to nonnormal data reported with medians. The means and standard deviations are as follows: for number of DWI, 7.0 (7.9) for SAH and 2.9 (2.0) for no SAH; for total volume, 7.5 (15.4) for SAH and 1.0 (1.8) for no SAH. The t-test has a P-value of .0168 for number of DWI and .039 for total volume. I suggest reporting the medians and Wilcoxon test from the table since the data are not normally distributed. View Large Among patients in the no-SAH group, DWI abnormalities were less common, antiplatelet use was more common. In addition, overall antiplatelet use prior to aneurysm treatment was associated with a significant decrease in incidence of DWI, but this effect was no longer significant on multivariate analysis. DWI Abnormalities and Outcomes Among all patients, those with a DWI abnormality were significantly less likely to have a good outcome (mRS 0-2) than patients without any DWI abnormality (95.6% vs 81.6%; P = .03). However, despite a higher overall rate of DWI in the SAH group, rates of symptomatic DWI were no different between the 2. Multivariate Analysis To assess which variables are independently associated with SAH or DWI, a multivariable logistic regression analysis was conducted on all covariates identified in baseline comparison, and a backward-stepwise approach was taken. The multivariable logistic regression identified 4-vessel angiogram (odds ratio [OR]: 82.2, confidence interval [CI] = [8.2, 821.1]), anterior communicating artery location (OR: 27.0, CI = [4.7, 154.3]), and DWI (OR: 15.8, CI = [3.9, 63.7]) as being independently associated with SAH. The multivariable logistic regression identified anterior communicating artery location (OR: 5.3, CI = [1.8, 15.1]) and, though not statistically significantly significant, mRS between 0 and 2 (OR: 0.24, CI = [0.1, 1.1]) as being independently associated with DWI. For these comparisons, an OR > 1 indicates a risk factor and OR < 1 indicates a protective factor. DISCUSSION Balloon Remodeling: Benefits and Drawbacks The technique of balloon-assisted coiling of intracranial aneurysms has been in use since 1999, with early literature on the technique demonstrating it to be effective in improving overall aneurysm occlusion rates.13 This technique has allowed for more effective coil embolization of anatomically difficult aneurysms, such as broad-neck aneurysms, as well as aneurysms in difficult locations, such as the middle cerebral artery.14,15 However, there are potential drawbacks to balloon use. Balloon inflation causes occlusion of anterograde flow so that the territory distal to the balloon inflation relies on indirect collateral supply. Structures supplied by perforators may be at higher risk of ischemia, as they lack robust collateral networks. In addition, the introduction of a balloon catheter, even if deflated, adds significant hardware to the intraluminal compartment and may incite thromboemboli.16 Although the early literature suggested that balloon-assisted coiling of cerebral aneurysms posited a higher risk of procedural complications,10 more recent literature has shown that balloon-assisted coiling is both safe and effective.17,18 In our own previous series, we have shown that use of the balloon in patients without SAH does not increase risk of procedural complications.11 However, there is some concern that use of the balloon in the setting of SAH may result in an increased incidence of complications, particularly ischemic events. Considerable work has been done to demonstrate that a consistent proinflammatory response exists following the rupture of an intracranial aneurysm,19,20,21 and that prothrombotic factors are elevated in this patient cohort. In a series of 681 patients with SAH, van Rooj et al10 showed that balloon use was significantly associated with thromboembolic complications. Santillan et al22 showed a trend toward higher rates of thromboembolic events in a group of SAH patients treated with balloon-assisted coiling as compared to unruptured patients, but the study was not powered to show a statistical significance. Balloon Remodeling and Ischemic Events Conventional wisdom endorses that repeated balloon inflations for aneurysm coil embolization in the setting of SAH may pose an undue risk of ischemic complications given the presumed systemic prothrombotic state of the critically ill SAH patient. However, studies to date have not been able to address this concern. What makes this dataset unique is the availability of the balloon inflation practice details (number of inflations, cumulative inflation time, etc.), postprocedure DWI imaging, and the fact that we have a control group of patients also treated with balloon remodeling, but in the unruptured setting (no SAH). In our series, we show a statistically significant increase in the overall number of DWI abnormalities in SAH patients with balloon remodeling compared to those without SAH treated with balloon remodeling. At first glance, these data might appear to support the notion that balloon use in the setting of SAH poses an undue risk of downstream emboli. However, a closer look reveals this not to be the case. There was no significant difference in the incidence of DWI abnormalities in the vascular territory distal to the treated aneurysm (and, hence, the site of balloon inflations). Furthermore, patients with aneurysms treated in the setting of SAH were much more commonly undergoing a complete cerebral angiogram. Together, these data provide evidence that these ischemic findings are unrelated to the use of the balloon, but perhaps are rather as a result of the complete diagnostic angiogram. While we cannot definitively conclude this from our dataset alone, we posit that these results are the byproduct of the widespread inflammatory and prothrombotic state that exists after SAH and that the catheter angiogram itself, as opposed to the devices used, represents the factor that places this patient cohort at risk for ischemic events.23 Of note, we expected antiplatelet use to be a protective factor against DWI events for the aforementioned reasons. While in our original analysis, patients on antiplatelets were significantly less likely to have a DWI (Table 2); this factor was not found to be significant on multivariate analysis. It may be that this association is present, but our study is not appropriately powered to detect such a difference. DWI Abnormalities and Outcome While most of the DWI abnormalities were silent events without clinical manifestation and the incidence of symptomatic DWI events (ie, those associated with a neurological deficit referable to a DWI abnormality seen on MRI) were the same between the SAH and no-SAH groups, a significant difference in outcomes was identified among patients with and without DWI abnormalities. Overall (SAH and no-SAH combined), patients with DWI abnormalities were less likely to have a good neurological outcome (mRS 0-2). This finding reinforces the idea that efforts aimed at reducing any DWI (silent or not) associated with aneurysm treatment are worthwhile in any patient population. Limitations Our paper has several limitations. First, this study was retrospective in nature. While the nature of the clinical practice between the SAH and no-SAH groups did not differ, the data sets for each groups were not captured prospectively. We do not have an a priori power analysis to demonstrate that our study is appropriately powered to detect the differences studied. Finally, we do not have MRI scans done prior to angiography, which means that we cannot exclude the possibility that these patients had pre-existing ischemic events as a result of the ictus as opposed to the intervention. Additionally, in retrospect, a comparison between the SAH group and a group of SAH patients treated without balloon assistance would be very valuable, but these data are not available to us. Additionally, due to the unique data parameters collected, we cannot easily find a historical institutional or literature cohort to use as a comparison. We make these limitations plain in this manuscript not to imply our findings to be hard truth but rather to demonstrate transparency in research. While our study is not perfect, we do have a unique data set that we believe is a positive addition to the literature and can prove useful in the decision-making process of the astute, informed neurovascular surgeon. CONCLUSION This study supports the use of balloon remodeling as a safe method of securing ruptured aneurysms in the SAH setting. Balloon use was not associated with a higher incidence of either silent or symptomatic ischemic events as identified on postprocedure MRI in the vascular territory distal to the aneurysm. Other factors, such as 4-vessel angiography or the SAH milieu itself, may be responsible for an overall increase in DWI abnormality seen in areas distant from the lesion. More concentrated study of these factors in the future could help elucidate the culprits responsible for the phenomena observed in the study of our patient cohort. Disclosures Dr Spiotta has the following conflicts of interest: Penumbra (consulting, honorarium, speaker bureau), Pulsar Vascular (consulting, honorarium, speaker bureau), Microvention (consulting, honorarium, speaker bureau, research), Stryker (consulting, honorarium, speaker bureau). Drs Turk, Turner, and Chaudry have the following conflicts of interest: Codman (consulting, honorarium, speaker bureau, research funding), Covidien (Consulting, Honorarium, Speaker Bureau), Penumbra (consulting, honorarium, speaker bureau, research grants), Microvention (consulting, honorarium, speaker bureau, research grants), Blockade (stock, consulting, honorarium, speaker bureau), Pulsar Vascular (stock, consulting, honorarium, speaker bureau, research), Medtronic (consulting, honorarium, speaker bureau). The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Zacharia BE, Hickman ZL, Grobelny BT et al.   Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin Am . 2010; 21( 2): 221- 233. Google Scholar CrossRef Search ADS   2. Miller BA, Turan N, Chau M, Pradilla G. Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage. Biomed Res Int . 2014; 2014: 384342. doi:10.1155/2014/384342. Google Scholar PubMed  3. Takizawa T, Tada T, Kitazawa K et al.   Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res . 2001; 23( 7): 724- 730. Google Scholar CrossRef Search ADS PubMed  4. Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost . 2005; 3( 10): 2185- 2192. Google Scholar CrossRef Search ADS PubMed  5. Prodan CI, Vincent AS, Kirkpatrick AC, Hoover SL, Dale GL. Higher levels of coated-platelets are observed in patients with subarachnoid hemorrhage but lower levels are associated with increased mortality at 30 days. J Neurol Sci . 2013; 334( 1-2): 126- 129. Google Scholar CrossRef Search ADS PubMed  6. Frontera JA, Aledort L, Gordon E et al.   Early platelet activation, inflammation and acute brain injury after a subarachnoid hemorrhage: a pilot study. J Thromb Haemost . 2012; 10( 4): 711- 713. Google Scholar CrossRef Search ADS PubMed  7. Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol . 2002; 88( 3): 227- 249. Google Scholar CrossRef Search ADS PubMed  8. Santillan A, Gobin YP, Mazura JC et al.   Balloon-assisted coil embolization of intracranial aneurysms is not associated with increased periprocedural complications. J Neurointerv Surg . 2013; 5( suppl 3): iii56- iii61. Google Scholar CrossRef Search ADS PubMed  9. Shapiro M, Babb J, Becske T, Nelson PK. Safety and efficacy of adjunctive balloon remodeling during endovascular treatment of intracranial aneurysms: a literature review. AJNR Am J Neuroradiol . 2008; 29( 9): 1777- 1781. 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Sato M, Nakai Y, Tsurushima H, Shiigai M, Masumoto T, Matsumura A. Risk factors of ischemic lesions related to cerebral angiography and neuro-interventional procedures. Neurol Med Chir (Tokyo) . 2013; 53( 6): 381- 387. Google Scholar CrossRef Search ADS PubMed  23. Santillan A, Gobin YP, Greenberg ED et al.   Intraprocedural aneurysmal rupture during coil embolization of brain aneurysms: role of balloon-assisted coiling. AJNR Am J Neuroradiol . 2012; 33( 10): 2017- 2021. Google Scholar CrossRef Search ADS PubMed  Acknowledgment Alyssa Pierce assisted with the editing and revision of this manuscript. Copyright © 2017 by the Congress of Neurological Surgeons

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NeurosurgeryOxford University Press

Published: Apr 1, 2018

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