Initial multicenter technical experience with the Apollo device for minimally invasive intracerebral hematoma evacuation.

TECHNIQUE ASSESSMENT

Initial Multicenter Technical Experience With the Apollo Device for Minimally Invasive Intracerebral Hematoma Evacuation BACKGROUND: No conventional surgical intervention has been shown to improve outcomes for patients with spontaneous intracerebral hemorrhage (ICH) compared with medical management. OBJECTIVE: We report the initial multicenter experience with a novel technique for the minimally invasive evacuation of ICH using the Penumbra Apollo system (Penumbra Inc, Alameda, California). METHODS: Institutional databases were queried to perform a retrospective analysis of all patients who underwent ICH evacuation with the Apollo system from May 2014 to September 2014 at 4 centers (Medical University of South Carolina, Stony Brook University, University of California at San Diego, and Semmes-Murphy Clinic). Cases were performed either in the neurointerventional suite, operating room, or in a hybrid operating room/angiography suite. RESULTS: Twenty-nine patients (15 female; mean age, 62 6 12.6 years) underwent the minimally invasive evacuation of ICH. Six of these parenchymal hemorrhages had an additional intraventricular hemorrhage component. The mean volume of ICH was 45.4 6 30.8 mL, which decreased to 21.8 6 23.6 mL after evacuation (mean, 54.1 6 39.1% reduction; P , .001). Two complications directly attributed to the evacuation attempt were encountered (6.9%). The mortality rate was 13.8% (n = 4). CONCLUSION: Minimally invasive evacuation of ICH and intraventricular hemorrhage can be achieved with the Apollo system. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology.

Alejandro M. Spiotta, MD* David Fiorella, MD, PhD‡ Jan Vargas, MD* Alexander Khalessi, MD§ Dan Hoit, MD¶ Adam Arthur, MDk Jonathan Lena, MD* Aquilla S. Turk, DOk M. Imran Chaudry, MDk Frederick Gutman, MD‡ Raphael Davis, MD‡ David A. Chesler, MD, PhD‡ Raymond D. Turner, MD* *Medical University of South Carolina, Department of Neurosciences, Division of Neurosurgery, Charleston, South Carolina; ‡Stony Brook University Medical Center, Department of Neurosurgery, Stony Brook, New York; §University of San Diego, Department of Neurosurgery, San Diego, California; ¶University of Tennessee, Department of Radiology, Memphis, Tennessee; kMedical University of South Carolina, Department of Radiology and Radiological Sciences, Charleston, South Carolina Correspondence: Alejandro M. Spiotta, MD, Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425. E-mail: [email protected] Received, September 26, 2014. Accepted, January 10, 2015. Published Online, February 14, 2015. Copyright © 2015 by the Congress of Neurological Surgeons.

KEY WORD: Intracerebral hemorrhage Operative Neurosurgery 11:243–251, 2015

S

pontaneous intracerebral hemorrhage (ICH) is responsible for 10% to 15% of strokes, with an annual incidence of 10 to 30 per 100 000 population.1,2 No conventional surgical intervention has been shown to improve outcomes compared with medical management.3 The most recent guidelines for the management of spontaneous ICH published by the American Stroke Association in 2007 recommend immediate surgery for cerebellar hemorrhages greater than 3 cm with evidence of brainstem compression or hydrocephalus and suggest considering ABBREVIATIONS: GCS, Glasgow Coma Scale; ICH, intracerebral hemorrhage; IVH, intraventricular hemorrhage; tPA, tissue plasminogen activator

OPERATIVE NEUROSURGERY

DOI: 10.1227/NEU.0000000000000698

a standard craniotomy for patients with lobar hemorrhages within 1 cm of the cortical surface.4 A minimally invasive approach to the evacuation of intracranial hematomas has been a topic of interest for some time. In 1989, Auer et al5 published their experiences with early endoscopic irrigation and aspiration-based evacuation of ICH. This trial demonstrated a significant improvement in 6-month mortality rate compared with medical management. More recently, the MISTIE II (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase II) trial showed a strong trend toward clinical benefit in patients with ICH treated with minimally invasive surgery followed by catheter drainage with daily recombinant tissue plasminogen activator (tPA) irrigation.

VOLUME 11 | NUMBER 2 | JUNE 2015 | 243

Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.

SPIOTTA ET AL

We report the initial multicenter experience with a novel technique for minimally invasive evacuation of intracerebral hematoma evacuation using the Penumbra Apollo system (Penumbra Inc, Alameda, California), a new low-profile, aspiration-irrigation system that has been recently approved by the US Food and Drugs Administration for the endoscopic aspiration of tissue and fluid in the ventricular system.

METHODS After approval by each center’s institutional review board, we conducted a retrospective review of charts and radiologic studies of all patients who experienced an intracranial hemorrhage and underwent hematoma evacuation with the Apollo system from May 2014 to September 2014 from 4 centers. Clinical data included age, sex, location of hemorrhage, depth of hemorrhage from the cortical surface, preprocedural hemorrhage volume, Glasgow Coma Scale (GCS) score, postprocedural hemorrhage volume and GCS score, whether the patient had been taking anticoagulation medications, time from presentation to surgery, length of hospital stay, and discharge disposition. Hemorrhage volume was calculated using the modified ellipsoid formula (length · width · height)/2. Length and width were measured on axial images, and coronal reconstructions were used to measure height. Indications for ICH evacuation with the Apollo device was at the discretion of the treating physician and generally included symptomatic space-occupying hematomas that were causing a local and/or global mass effect. External ventricular drains were placed depending on clinical need, and the hematoma evacuation was done as a separate procedure.

Procedural Technique All procedures were performed by a neurosurgeon alone or an interventional neuroradiologist in combination with a neurosurgeon with patients under general endotracheal anesthesia. Procedures were performed either in the neurointerventional suite, operating room, or in an intraoperative angiography suite. The patients were either placed in a Mayfield headholder or a reference array was attached directly to the skull and the preoperative head computed tomography or magnetic resonance imaging data were registered to the patient using a stereotactic neuronavigation system (Brainlab, Feldkirchen, Germany). For procedures performed in the neurointerventional suite without endoscopy, Brainlab instrument adapter arrays were attached to the Apollo wand and twist drill. With neuronavigational guidance, a planned skull entry site was marked. The access site was planned using a trajectory along the long axis of the hematoma and/or the ventricle casted with hemorrhage, avoiding eloquent cortex. The surgical site was prepped and draped in a sterile manner, and a small stab incision was made. A twist drill craniotomy hole was created. For procedures in which a sheath was used, an 8-French sheath was trimmed to a length that would access the most superficial aspect of the hematoma and then left in place for the hematoma evacuation. The Apollo wand was advanced through the sheath into the hematoma under neuronavigation, and the hematoma was aspirated using the 2.6-mm Apollo wand with intermittent irrigation as required. Serial DynaCT (Siemens Medical, Erlangen, Germany) images were obtained intraprocedurally to assess the volume of clot remaining. Once a significant reduction in hematoma volume had been achieved, the Apollo wand was removed, and the incision was closed. For procedures performed with endoscopy in addition to neuronavigation, a 14-mm burr hole was created using a high-speed drill. A 19-

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to 20-French peel away sheath was attached to an array, registered, and placed using neuronavigation in the ICH. Clot aspiration was performed under direct visualization using the 2.6-mm Apollo Wand through the endoscopic working channel of a Karl Storz LOTTA endoscope (Tuttlingen, Germany). In some procedures, the endoscope was registered to the neuronavigation system. In other cases, the endoscopic sheath was registered. In procedures performed in the angiography suite, intraprocedure DynaCT was used to evaluate for residual clot and, when required, DynaCT data were uploaded to the neuronavigation system to provide an optimized trajectory into the remaining clot. In procedures performed within a standard operating room, cone-beam computed tomography (CT) was not available, and so the extent of clot aspiration was determined by direct endoscopic visualization and an estimation of the hemorrhage volume evacuated. All patients were transferred to the neurosciences intensive care unit postprocedurally for close neurological and hemodynamic monitoring.

RESULTS Patient Demographics Twenty-nine patients (15 female patients; mean age 62 6 12.6 years) underwent procedures between May and September 2014 at 4 institutions (Table 1). Patients presented with a GCS score of 3 to 5 (n = 4), 6 to 8 (n = 6), 9 to 12 (n = 10), and 13 to 15 (n = 9). The location of the ICH included lobar (n = 15; occipital, parietal, temporal, and frontal), basal ganglia (n = 13), and brainstem (n = 1). Six of these had an additional IVH component. Two cases were associated with aneurysmal rupture and subarachnoid hemorrhage and were treated immediately after coil embolization of the index aneurysm; the remainder were presumed to be spontaneous hemorrhages. Eleven patients were taking some form of anticoagulation or were coagulopathic at the time of presentation (aspirin, n = 4; clopidogrel [Plavix], n = 1; warfarin [Coumadin], n = 4; rivaroxaban [Xarelto], n = 1; acquired factor VIII inhibitor, n = 1). The mean volume of ICH was 45.4 6 30.8 mL (range, 8.7-114 mL) with a mean depth from the cortical surface of 2.2 6 1.8 cm (range, 0-8.1 cm). ICH Evacuation Time from symptom onset to intervention was 2.3 6 3.2 days. Eighteen (62%) of the procedures were performed with endoscopic visualization; all but 1 was performed with intraprocedural neuronavigation. The single procedure performed without neuronavigation involved a superficial rehemorrhage after an open craniotomy for evacuation of the original hematoma. Twenty-four of the procedures (83%) were performed in the neurointerventional suite, and the remainder performed in the operating room. Intracranial access was obtained with a burr hole in 17 patients and with a craniotomy twist drill in 12. Two complications directly attributed to the evacuation attempt were encountered (6.9%). One procedure resulted in an immediate increase in the ICH and IVH volume. In another case, there was a delayed (12 hours) rehemorrhage and worsening of the cerebral edema requiring a decompressive craniotomy.

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APOLLO DEVICE

TABLE 1. Preprocedural Demographic Characteristicsa Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 a

Sex

Age, y

Location

Depth From Surface, cm

Anticoagulation

F M F M M F M M M M F F M M F M F F F F F M F M

56 50 67 75 71 42 66 54 41 51 63 55 49 60 63 79 56 43 59 59 62 54 83 60

Right occipital Left thalamus Left gyrus rectus Right BG/thalamus/IVH Right BG, carotid terminus Left BG/IVH Left BG/thalamus/IVH Left BG/thalamus/IVH Right BG Right BG Left BG Right BG Left parietal lobe Brainstem Left BG Right hemisphere Left BG Right BG/IVH Right frontoparietal Right frontoparietal Left frontal Left frontoparietal Right frontal Left frontal

0.4 3.5 1.4 2.0 1.6 2.5 3.8 2.0 2.8 1.8 1.5 1.7 0.5 4.5 3.0 2.0 6.0 5.0 2.0 1.0 1.0 0.5 0.0 8.1

Baby aspirin Baby aspirin Xarelto (rivaroxaban) Coumadin (warfarin) None Plavix (clopidogrel) None None None None None Aspirin None None None Aspirin None None None Coumadin (warfarin) Factor VIII inhibitor None None None

F, female; M, male; BG, basal ganglia; IVH, intraventricular hemorrhage.

After the evacuation procedure, the mean ICH volume decreased to 21.8 6 23.6 mL (mean, 54.1% 6 39.1% reduction; P , .001) (Table 2). We defined treatment failure as a volume reduction ,20%, which occurred in 3 patients (10.3%). In 1 patient, it involved placement of a catheter in the evacuation cavity and tPA administration, resulting in hematoma expansion, and another occurred in another patient who was taken to the operating room for a craniotomy and hematoma evacuation immediately after attempted Apollo aspiration. Outcomes The mortality rate of this population was 13.8% (n = 4). At the time of manuscript submission, 2 patients were discharged home, 12 to an acute rehabilitation center, 2 to long-term care facilities, and 9 patients are currently awaiting discharge from the hospital. There were no significant differences between patients with lobar hemorrhages and basal ganglia hemorrhages (Table 3).

ILLUSTRATIVE CASES Patient 2 A 50-year-old hypertensive patient presented with the acute onset of slurred speech and right upper extremity weakness (3/5 strength), with a systolic blood pressure in the 200s. Head CT


showed a left-sided thalamic hemorrhage with intraventricular extension (Figure 1A). CT angiography showed no vascular lesion or “spot sign.” The following day, hematoma evacuation was performed with the Apollo system (Figure 1B). An external ventricular drain was left in the left occipital horn and clamped. Postoperatively the patient’s headache and hemiparesis completely resolved. He was monitored in the intensive care unit for a day and then transferred to the floor. He was discharged home on hospital day 4 neurologically intact (Figure 1C). Patient 4 An elderly man with a history of atrial fibrillation treated with warfarin was found unresponsive by his family. His presenting National Institutes of Health Stroke Scale score was 29. On examination, the patient demonstrated left-sided hemiparesis as evidenced by flexor posturing and was localizing with the right upper extremity and withdrawing in the right lower extremity. The admission international normalized ratio was 3. CT and CT angiography showed a massive right-sided basal ganglia hemorrhage with no underlying vascular malformation (Figure 2A). The patient’s anticoagulation was emergently reversed, and he was taken to the angiography suite where he underwent evacuation of his hematoma. A drain was left in place (Figures 2B and 2C).



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TABLE 2. Pre- and Postprocedural Detailsa Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 a


b

Time to Treatment, days

Endoscope

OR vs Angio

Preprocedure Volume, mL

Postprocedure Volume, mL

Reduction, %

Prepro cedure GCS Score

Postprocedure GCS Score

LOS, d

Disposition

0.8 1.0 0.5 0.0 0.4 0.3 0.5 3.8 1.0 16.0 9.0 2.0 2.0 1.0 3.0 4.0 2.0 1.0 2.0 2.0 1.0 0.5 1.0 2.0

Yes Yes No No No No No No Yes Yes Yes No No No No Yes Yes Yes Yes Yes Yes Yes Yes Yes

OR OR Angio Angio Angio Angio Angio Angio OR OR OR Angio Angio Angio Angio Angio Angio Angio Angio Angio Angio Angio Angio Angio

25.8 9.7 8.8 114.6 29.4 46.1 10.2 47.9 33.8 29.0 32.3 21.0 53.9 8.2 36.2 90.0 16.0 15.0 78.0 30.0 46.0 59.5 53.4 128.0

15.3 6.0 3.1 48.9 4.9 18.9 3.8 29.1 12.0 4.2 2.0 17.3 33.3 3.0 59.6 11.2 0.7 0.0 8.0 10.0 39.0 33.1 20.2 65.0

40.7 37.8 64.7 57.3 83.2 59.1 63.0 39.3 65.0 85.0 94.0 17.4 38.2 63.7 264.6b 87.6 95.6 100.0 89.7 66.7 15.2 44.4 62.2 49.2

9 15 4 7 12 7 11 10 6 14 11 14 11 3 13 14 15 3 14 14 7 11 7 11

9 15 8 10 11 3 10 10 12 14 11 15 12 4 14 15 4 6 15 2 7 10 8 11

56 4 17 12 20 1 Ongoing Ongoing 29 31 18 4 Ongoing Ongoing 22 14 9 30 30 11 10 Ongoing Ongoing 4

LTAC Home Rehab Death Rehab Death

OR, operating room; Angio, angiography; GCS, Glasgow Coma Scale; LOS, length of stay; LTAC, long term acute care facility; Rehab, rehabilitation; SNF, skilled nursing facility. Immediate increase in hemorrhage volume with intraventricular hemorrhage.


SNF Rehab Rehab Rehab

Rehab Rehab Rehab Rehab Rehab Rehab Death

Home

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TABLE 3. Comparison Between Patients With Lobar and Basal Ganglia Hemorrhagesa BG (n = 14)

Lobar (n = 14)

56.3 6 36.4 15.2

67.9 9 57.1 29.8

.071 .104

58.9 10.14 10.3 13.6b

48.5 10.3 9.8 17.9c

.500 .918 .771 0.807

Mean age, y Female Mean pretreatment volume, mL Mean posttreatment volume, mL Reduction, % Pretreatment GCS score Posttreatment GCS score Length of stay, d Disposition Home Rehabilitation SNF LTAC Death Ongoing

1 7 1 0 2 3

P Value .013

1 5 0 1 2 5

a

BG, basal ganglia; GCS, Glasgow Coma Scale; SNF, skilled nursing facility; LTAC, long term acute care facility. b n = 11. c n = 9.

Postoperatively, he was following commands with the right, but still flexing on the left. His drain was removed on postoperative day 6. His course was complicated by the development of a pneumonia that prevented him from being weaned from the ventilator. At this point, his family elected to transition him to comfort care, and the patient died on postoperative day 11. Patient 5 An elderly man presented with expressive aphasia, facial droop, and right-sided hemiparesis. He was able to follow commands on

the left side. Head CT and CT angiography showed a left frontal intraparenchymal hemorrhage with an associated left-sided internal carotid artery terminus aneurysm measuring 7 · 4 mm (Figures 3A and 3B). A ventriculostomy was placed. The patient was intubated and taken to the angiography suite where the left carotid terminus aneurysm was coiled (Figures 3C and 3D). Once this was completed, the patient underwent a left-sided twist drill craniotomy for evacuation of hematoma (Figure 3E). Both procedures were uncomplicated. On postprocedure examination, the patient improved to the point where he was able to follow commands in all 4 extremities, with full strength on the right side and 4/5 strength on the left side (Figure 3F). He was successfully extubated on postoperative day 2 and was transferred out of the intensive care unit on postoperative day 4. On postoperative day 9, the patient became more confused and somnolent, and a CT angiogram was concerning for vasospasm. The patient was transferred back to the ICU for treatment of vasospasm. By hospital day 11, examination showed that he had improved to the point where he was confused but able to follow commands antigravity with all 4 extremities. He underwent placement of a ventriculoperitoneal shunt on hospital day 14. By hospital day 21, he was oriented to place and person and was following commands; he was discharged to acute rehabilitation.

DISCUSSION Spontaneous Intracranial Hemorrhage Intracranial hemorrhages account for 15% to 20% of strokes and are associated with a mortality rate of .40%.6 The neurological injury is thought to be not only due to the immediate mechanical disruption caused by the original hemorrhage, but also by the accumulation of perihematomal edema secondary to an inflammatory reaction incited by hemoglobin

FIGURE 1. Patient 2 with left basal ganglia intracranial hemorrhage. A, initial noncontrast head computed tomography (CT). B, noncontrast head CT on postoperative day 1. A ventriculostomy catheter is in place in the surgical bed, and there is a decrease in overall mass effect. C, noncontrast head CT on postoperative day 3.




SPIOTTA ET AL

FIGURE 2. Patient 4, who is taking Coumadin (warfarin) was brought to the emergency department after being found down. A, initial noncontrast head computed tomography (CT) demonstrating a large right-sided intracranial hemorrhage. B, noncontrast head CT on postoperative day 1 demonstrating decrease in hematoma volume with a ventriculostomy catheter. C, noncontrast head CT on postoperative day 4 demonstrating a further decrease in hematoma volume.

breakdown products and the presence of thrombin. This second phase of injury results in the extension of damage to potentially viable tissue.2,7-9 Animal models have demonstrated that early removal of cerebral hematomas can lead to improved late outcomes by improving regional perfusion.10 Despite the theoretical benefits of early hematoma evacuation, the STITCH (Surgical Trial in Intracerebral Hemorrhage) failed to show any overall benefit of early surgery compared with conservative management for patients with supratentorial ICH.3 However, a subgroup analysis of the STITCH data suggested that favorable outcomes were more likely with surgery performed on hematomas ,1 cm from the cortical surface.11 These findings led to the STITCH II, which similarly failed in its primary endpoint to show a benefit of the surgical evacuation of superficial lobar hemorrhages. Again, a subgroup analysis showed a benefit of early surgery in patients with a poor prognosis (large hemorrhage, older age, poor presenting neurological status) and superficial hematomas without intraventricular extension.12 A subsequent meta-analysis of 14 trials of surgery for intracerebral hemorrhage demonstrated improved outcomes with surgery if randomization was performed within 8 hours of hemorrhage, if the volume of hematoma was between 20 and 50 mL, if the Glasgow Coma Scale score was 9 to 12, or if patient age was between 50 and 69 years.13 When the results of the STITCH II were pooled with these data, the subgroup of patients with lobar intracranial hemorrhage and no IVH demonstrated a trend toward a benefit of surgery, but this trend was not significant.12 The authors of the STITCH II conclude that these the existing data suggest a potential role for surgery in ICH, but it remains unclear which patient cohort(s) would benefit. Minimally Invasive Interventions The results of the STITCH suggested that although surgery may improve outcomes in some patients with lobar hemorrhages


that were within 1 cm of the cortical surface, for lesions deeper within the brain, attempts at evacuation are thought to disrupt viable tissue and overcome any benefits yielded by hematoma removal. There are several reports of the use of stereotactic minimally invasive techniques such as direct aspiration and mechanical clot disruption to safely remove deeper hemorrhages.5,14-17 More recently, newer methods for hematoma disruption have been introduced, such as ultrasound and injection of recombinant tPA directly into the hematoma.18,19 In the MISTIE trials, a strategy of minimally invasive surgery followed by tPA infusion and catheter drainage was compared with standard medical management. In the MISTIE trial, the surgical procedure reduced perihematomal edema and demonstrated a trend toward better 365-day clinical outcomes as well as reduced lengths of hospital stay.18 The CLEAR II (Clot Lysis Evaluating Accelerated Resolution of IVH Phase II) trial aimed to investigate the benefit of clearing intraventricular blood in the setting of spontaneous ICH or subarachnoid hemorrhage.20 IVH has been shown to be an independent risk factor for poor outcome and occurs in 40% to 45% of ICHs.11,21,22 The patients who received intraventricular recombinant tPA showed a trend toward lower mortality at 30 days (18% vs 23% in placebo groups); however, this was not statistically significant. There was a significant relationship observed with respect to the rate of clot resolution and clinical improvement at 96 hours. In addition, a greater percentage of patients treated with intraventricular tPA demonstrated a modified Rankin Scale score #4 (52% vs 27%) and a National Institutes of Health Stroke Scale score ,10 (54% vs 29%) at 30 days. Although the trial was not powered to assess functional outcomes, it demonstrated the safety of a minimally invasive approach to the treatment of IVH and paved the way for the launch of the CLEAR III trial.



APOLLO DEVICE

FIGURE 3. Patient 5 with a ruptured left internal carotid artery terminus aneurysm associated with an intraparenchymal hematoma. A, initial noncontrast head computed tomography (CT) demonstrating a large left-sided intraparenchymal hematoma with midline shift. B, coronal reconstruction of a CT angiogram demonstrating a left internal carotid artery aneurysm with an overlying hematoma. C, digital subtraction angiography with an anteroposterior projection of a left internal carotid injection demonstrating the morphology of the aneurysm. D, digital subtraction angiography with an anteroposterior projection of a posttreatment left internal carotid injection. E, screenshot of Brainlab screen demonstrating planned trajectories for hematoma evacuation. F, noncontrast head computed tomography on postoperative day 1 demonstrating resolution of mass effect and midline shift.

The Apollo system offers several important advantages compared with the techniques used in the MISTIE and CLEAR trials. The Apollo can achieve an immediate evacuation of the majority of the hematoma at the time of the procedure without the need for prolonged thrombolytic irrigation and catheter drainage, as shown in the MISTIE and CLEAR II trials, where the average length of treatment was 3.9 days and 10.2 days, respectively. The injection of thrombolytic chemicals into the parenchymal or ventricular space may have harmful effects. In the CLEAR II trial, 6 of 26 patients (23%) treated with intraventricular tPA experienced a symptomatic bleeding event, 4 of whom required neurosurgical intervention. Although the benefits of intraventricular tPA in ischemic stroke have been proven, animal models have demonstrated that there are cytotoxic side effects that are still poorly understood.23-27 Furthermore, immediately removing the hematoma with the Apollo system, as opposed to the several days often


required with pharmacological thrombolysis and catheter drainage strategy, may have significant advantages with respect to efficiently improving regional perfusion and reducing the potential deleterious effects related to the breakdown of large volumes of parenchymal blood products. ICH Caused by Aneurysmal Rupture The classic teaching of the management of a parenchymal hemorrhage from a ruptured aneurysm with significant mass effect and neurological symptoms has been open surgical evacuation with clipping of the aneurysm. In our series, 3 patients had a parenchymal hemorrhage from a ruptured aneurysm. In these patients, the aneurysm was treated endovascularly and the hemorrhage was evacuated either immediately after or the following day in the angiography suite using the Apollo system. The benefits to this approach include combining the advantages of



SPIOTTA ET AL

endovascular coiling with a minimally invasive hematoma evacuation procedure, sparing the patient from being transported to the operating room in some cases and undergoing an invasive craniotomy. This strategy could allow patients to benefit from an endovascular rather than a surgical approach to aneurysm occlusion,28,29 as these patients would otherwise undergo surgical clipping at the time of craniotomy for ICH evacuation. In addition, aneurysmal intracranial hemorrhages seem to be conceptually well suited to evacuation with the Apollo system. The rupture of an aneurysm creates a hematoma that dissects through the brain parenchyma, typically creating a discrete, welldemarcated parenchymal hemorrhage that is under local pressure and thereby lends itself to evacuation through the working sheath. Apollo Experience The Apollo system has been currently cleared for use in the United States for the removal of blood and tissue from the ventricular system. As such, the reported application of this system for the minimally invasive evacuation of intraparenchymal hematomas represents an off-label use. Our early multicenter experience demonstrates a 91.7% technical success rate, with significant reduction in the hematoma size from 45 mL to 21 mL on average. This is noteworthy because this is close to the recommended surgical endpoint of the recently launched MISTIE III trial (15-20 mL). Overall, the mortality rate for this population was low (13.8%) considering these patients presented with relatively large ICH volumes that were most commonly in deepseated locations such as the basal ganglia. Limitations This is a retrospective case series from several institutions and as such has several limitations. The small sample size introduces bias and limits any statistical analysis performed and any conclusions drawn. Furthermore, because of the novelty of this procedure, there was no standardization across institutions as to the timing of repeat imaging to assess for hematoma stability, timing from presentation to procedure, and operative technique, as some institutions preferred the use of neuroendoscopy instead of relying solely on neuronavigation.

CONCLUSION Minimally invasive evacuation of ICH and IVH can be achieved with the Apollo system. This represents a potentially important advance for this patient population in whom surgical and medical treatment options are limited. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology. Disclosures Drs Turner, Turk, Chaudry, and Spiotta have received research funding, honoraria, and consultation fees from the following companies: Microvention, Penumbra, Covidien, Siemens, Pulsar, Medpace, and Stryker. Dr Hoit is a consultant


for Penumbra. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

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22. Hallevi H, Albright KC, Aronowski J, et al. Intraventricular hemorrhage: Anatomic relationships and clinical implications. Neurology. 2008;70(11):848-852. 23. Wang X, Asahi M, Lo EH. Tissue type plasminogen activator amplifies hemoglobin-induced neurotoxicity in rat neuronal cultures. Neurosci Lett. 1999; 274(2):79-82. 24. Tabrizi P, Wang L, Seeds N, et al. Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background. Arterioscler Thromb Vasc Biol. 1999;19:2801-2806. 25. Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, Lipton SA. Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med. 1998;4:228-231. 26. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587. 27. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. 28. McDougall CG, Spetzler RF, Zabramski JM, et al. The Barrow ruptured aneurysm trial. J Neurosurg. 2012;116(1):135-144. 29. Molyneux A, Kerr R; International Subarachnoid Aneurysm Trial Collaborative Group, , et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial. J Stroke Cerebrovasc Dis. 2002;11(6):304-314.

COMMENTS

I

ntracerebral hemorrhage carries an unacceptably high 30-day mortality of 40%. Currently there is no therapeutic intervention that has proved to be effective in decreasing the mortality and in improving the outcomes of intracerebral hemorrhage. Consensus from a limited number of clinical studies is gravitating toward intracerebral hematoma volume reduction as an effective therapeutic approach. The authors of the current study have done a good job in presenting the initial multicenter experience with a novel minimally invasive technique for intracerebral hematoma evacuation using the US Food and Drug Administration–approved Penumbra Apollo irrigation-aspiration system. The most significant result of this initial experience is the technical success of the Apollo system, which achieved a clot volume reduction of 54%, similar to the clot volume reduction of 62% in the MISTIE II trial. Being a retrospective analysis of the experiences at different centers, this study has obvious limitations that need to be addressed in future studies. Patient selection, standardization of operative procedure, timing of procedure, and outcome measures are some of the factors that need to be considered in the design of future prospective studies using this system. Overall, the use of the Apollo system minimally invasive approach is a laudable effort that nonetheless should be taken in the context of other minimally invasive approaches such as the MISTIE III trial, which is currently ongoing. Obviously not every patient in whom an intracerebral hemorrhage develops will qualify for the MISTIE III trial. In the design of future


clinical studies using the Apollo system, it would be useful to determine whether patients who do not meet the inclusion criteria for MISTIE III can be treated using the Apollo minimally invasive approach. Perhaps these minimally invasive approaches to intracerebral hematoma evacuation will lead to the development of effective tools for the treatment of this condition, which continues to pose a conundrum for the neurosurgical community. Jody Leonardo Cletus Cheyuo Amherst, New York

T

he authors present their retrospective multicenter series of 29 patients with space-occupying intraparenchymal hemorrhages treated by minimally invasive evacuation with the Penumbra Apollo system. The results are exciting: 92% technical success rate, significant reduction in mean hematoma volume from 45 to 21 mL, and only a 14% mortality rate. Confirmatory prospective studies using Apollo technology are the next step in evaluating the safety and efficacy of aspiration for hematoma evacuation. The Apollo system is an exciting new technology that allows stereotactic, minimally invasive hematoma aspiration through a single bur hole without the need for catheter implantation or administration of thrombolytic agents. For these reasons, the technique may allow for shorter intensive care unit lengths of stay and reduced rehemorrhage rates compared with the techniques used in the MISTIE or CLEAR trials. Further, these procedures may be performed in either an operating room or an angiography suite with computed tomography capability. In fact, the availability of CT imaging in modern angiography suites may make the angiography suite the preferred location for these procedures, as the extent of hematoma evacuation can be assessed with serial CT imaging intraprocedurally, multiple times if needed, to confirm procedural success. Spontaneous intraparenchymal hemorrhages remain a devastating disease. Although minimally invasive hematoma evacuation remains an unproven treatment strategy for parenchymal hemorrhages, there is growing support for these techniques among the neurosurgical community, with many expecting the ongoing trials to eventually provide the definitive evidence supporting stereotactic hematoma evacuation over medical management. The investigators should be congratulated for their efforts in pushing this exciting technology forward. Kyle M. Fargen Gainesville, Florida J Mocco New York, New York



Novel device and technique for minimally invasive intracerebral hematoma evacuation in the same setting of a ruptured intracranial aneurysm: combined treatment in the neurointerventional angiography suite.

Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation (Mi SPACE) for Intracerebral Hemorrhage.

Chronic Encapsulated Intracerebral Hematoma: Endoscopic Removal as Minimally Invasive Surgery for a Patient with Alcoholic Cirrhosis.

Factors affecting the evacuation rate of intracerebral hemorrhage in basal ganglia treated by minimally invasive craniopuncture.

Minimally invasive surgery for intracerebral haemorrhage.

Evacuation of hypertensive intracerebral hematoma by a stereotactic technique.

Effects of minimally invasive procedures for evacuation of intracerebral hematoma in early stages on MMP-9 and BBB permeability in rabbits.

Beginner Surgeon's Initial Experience with Distal Subtotal Gastrectomy for Gastric Cancer Using a Minimally Invasive Approach.

Minimally invasive endoscopic surgery for treatment of spontaneous intracerebral haematomas.

Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats.

Initial experience with internal mammary artery harvesting with the da Vinci Surgical System for minimally invasive direct coronary artery bypass.

Spontaneous intracerebral and intraventricular hemorrhage: advances in minimally invasive surgery and thrombolytic evacuation, and lessons learned in recent trials.

The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats.

Minimally invasive management of retropubic bleeding and hematoma evacuation after a TVT Secur or mini-sling procedure.

Preliminary experience with the Pipeline Flex Embolization Device: technical note.

Minimally invasive thymectomy: the Mayo Clinic experience.

Minimally invasive cone beam CT-guided evacuation of parenchymal and ventricular hemorrhage using the Apollo system: proof of concept in a cadaver model.

Robotic assisted minimally invasive esophagectomy (RAMIE): the University of Pittsburgh Medical Center initial experience.

Minimally invasive ventricular assist device surgery.

Minimally invasive surgery for pediatric trauma-a multicenter review.

Effects of intracerebral hemorrhage and subsequent minimally invasive hematoma aspiration on expression of apoptosisrelated genes in rats.

Minimally Invasive Surgical Treatment of Acute Epidural Hematoma: Case Series.

Mild hypothermia in combination with minimally invasive evacuation of hematoma reduces inflammatory damage in patients via the nuclear factor-κB pathway.

Minimally-invasive liver resection in pediatric patients: initial experience and outcomes.