8-F balloon guide catheter for embolization of anterior circulation aneurysms: an institutional experience in 152 patients.

The use of 8-F balloon guide catheter (BGC) for proximal flow control was previously shown to prevent distal embolic complications during mechanical clot retrieval in patients with acute ischemic stroke. In this retrospective study, the utility of 8-F BGCs for proximal flow control during endovascular coiling of anterior circulation aneurysms was investigated. Patients who underwent endovascular coiling for anterior circulation aneurysms between August 2013 and December 2016 were retrospectively analyzed. Among a total of 152 patients included in this series, 64 patients presented with aneurysmal rupture, whereas the aneurysms were detected incidentally or due to mass effects in the remaining patients. 8-F BGCs were successfully navigated in all patients. The balloon was inflated during navigation in 19 patients. Inflation of the catheter balloon during coil embolization was required in 34 patients; this was performed as an emergency maneuver in six of these patients. Thromboembolic complications occurred in one patient. 8-F BGC can be effectively used for proximal flow control during endovascular treatment of anterior circulation aneurysms. The other advantages included improved navigation of tortuous arterial anatomy, coil stabilization during aneurysmal coiling, and freedom to utilize aneurysmal neck-remodeling balloons for additional adjunctive techniques or to deploy rescue stents. This novel approach might be safely and effectively used in patients undergoing endovascular treatment for anterior circulation aneurysms.

A case of anterior communicating artery aneurysm successfully treated after a stent migration during stent assisted endovascular coil embolization.

Stent migration is a complication associated with endovascular coil embolization of intracranial aneurysms. We report a case of anterior communicating artery (ACoA) aneurysm that was successfully treated after stent migration during endovascular coil embolization without retrieval of the stent. A 47-year-old man presented with sudden onset severe headache. Patient was noted to have subarachnoid hemorrhage from a ruptured ACoA aneurysm. Emergency endovascular coil embolization was performed. The second coil embolization was scheduled for the neck-remnant portion with a stent after 16 days from the initial operation. At first, a stent was deployed from the right perpendicular division of anterior cerebral artery (A2) to the left horizontal division of anterior cerebral artery (A1) entirely across the aneurysmal neck. Although the stent position looked fine, the stent migrated inferiorly to the proximal A1 portion when its delivery wire was withdrawn. Fortunately, the stent could be pushed into the distal A1 portion, when we trying to re-access the aneurysm thorough the stent with a pig-tail shaped microguidewire. Additional coil embolization was achieved using the assistance of distal tip of the stent as a scaffold of the coil. The patient was discharged without any complication on the postoperative day 6. Although there are various choices of rescue treatment after stent migration, this is the first reported case of stent repositioning with a microguidewire. Our technique may represent an effective option in case of stent migration.

Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria.

BACKGROUND: Recent guidelines for endovascular management of emergent large vessel occlusion (ELVO) award top tier evidence to the same selective criteria in recent trials. We aimed to understand how guideline adherence would have impacted treatment numbers and outcomes in a cohort of patients from a comprehensive stroke center. METHODS: A retrospective observational study was conducted using consecutive emergent endovascular patients. Mechanical thrombectomy (MT) was performed with stent retrievers or large bore clot aspiration catheters. Procedural outcomes were compared between patients meeting, and those failing to meet, top tier evidence criteria. RESULTS: 126 patients receiving MT from January 2012 to June 2015 were included (age 31-89 years, National Institutes of Health Stroke Scale (NIHSS) score 2-38); 62 (49%) patients would have been excluded if top tier criteria were upheld: pretreatment NIHSS score <6 (10%), Alberta Stroke Program Early CT score <6 (6.5%), premorbid modified Rankin Scale (mRS) score ≥2 (27%), M2 occlusion (10%), posterior circulation (32%), symptom to groin puncture >360 min (58%). 26 (42%) subjects had more than one top tier exclusion. Symptomatic intracerebral hemorrhage (sICH) and systemic hemorrhage rates were similar between the groups. 3 month mortality was 45% in those lacking top tier evidence compared with 26% (p=0.044), and 3 month mRS score 0-2 was 33% versus 46%, respectively (NS). After adjusting for potential confounders, top tier treatment was not associated with neurological improvement during hospitalization (ß -8.2; 95% CI -24.6 to -8.2; p=0.321), 3 month mortality (OR=0.38; 95% CI 0.08 to 1.41), or 3 month favorable mRS (OR=0.97; 95% CI 0.28 to 3.35). CONCLUSIONS: Our study showed that with strict adherence to top tier evidence criteria, half of patients may not be considered for MT. Our data indicate no increased risk of sICH and a potentially higher mortality that is largely due to treatment of patients with basilar occlusions and those treated at an extended time window. Despite this, good functional recovery is possible, and consideration of MT in patients not meeting top tier evidence criteria may be warranted.

The first North American use of the Pipeline Flex flow diverter.

Flow diversion for the management of intracranial aneurysms represents a paradigm shift in how aneurysms are managed. The Pipeline embolization device (PED) is, to date, the only flow diverter approved for use in the USA by the Food and Drug Administration. Limitations and complications with new treatment strategies are inevitable, and with the PED there have been reports of complications, most commonly with challenging deployments. Once deployment has been initiated, the device is 'one-way'; it can only be deployed further or removed. Yet, situations arise in which the ability to recapture or reposition the device would be advantageous. A second-generation Pipeline has been developed that addresses these concerns. We report the first use in North America of this second-generation Pipeline device: the Pipeline Flex. We discuss our rationale for using the device, our impressions of its operation, and the relevant literature concerning the current state of flow diversion.

The first North American use of the Pipeline Flex flow diverter.

Flow diversion for the management of intracranial aneurysms represents a paradigm shift in how aneurysms are managed. The Pipeline embolization device (PED) is, to date, the only flow diverter approved for use in the USA by the Food and Drug Administration. Limitations and complications with new treatment strategies are inevitable, and with the PED there have been reports of complications, most commonly with challenging deployments. Once deployment has been initiated, the device is 'one-way'; it can only be deployed further or removed. Yet, situations arise in which the ability to recapture or reposition the device would be advantageous. A second-generation Pipeline has been developed that addresses these concerns. We report the first use in North America of this second-generation Pipeline device: the Pipeline Flex. We discuss our rationale for using the device, our impressions of its operation, and the relevant literature concerning the current state of flow diversion.

Neuroprotective effect of darbepoetin alfa, a novel recombinant erythropoietic protein, in focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for treating anemia. In animal models, exogenous recombinant human erythropoietin has been reported to be beneficial in treating experimental cerebral ischemia. In this study, we determined whether darbepoetin alfa would protect in a rat model of transient focal cerebral ischemia. METHODS: Rats received 2-hour middle cerebral artery suture-occlusion. The drug (darbepoetin alfa, 10 microg/kg) or vehicle was administered intraperitoneally 2 hours after onset of middle cerebral artery occlusion. Animals were allowed to survive for 3 or 14 days. Behavioral tests were performed sequentially. Infarct volumes and brain swelling were determined. RESULTS: Darbepoetin alfa-treated rats showed improved neuroscores relative to vehicle-treated animals beginning within 1 hour of treatment and persisting throughout the 14-day survival period. Darbepoetin alfa significantly reduced corrected total (cortical + subcortical) infarct volume (56.3+/-20.6 and 110.8+/-6.8 mm3, respectively) and total infarct areas at multiple levels compared with vehicle in the 14-day survival group. Brain swelling was not affected by treatment. CONCLUSIONS: Darbepoetin alfa confers behavioral and histological neuroprotection after focal ischemia in rats.

Caffeinol confers cortical but not subcortical neuroprotection after transient focal cerebral ischemia in rats.

The combination of low-dose ethanol and caffeine (caffeinol) protects cortical areas of the brain from damage produced by distal focal ischemia in rats. There are no data, however, as to whether caffeinol influences injury in subcortical brain regions. Rats were anesthetized with halothane and subjected to 2 h of MCAo by poly-l-lysine-coated intraluminal suture. Caffeinol [a combination of ethanol, 0.33 g/kg, and caffeine, 10 mg/kg (n=5)] or vehicle (0.9% NaCl; n=7) was administered by i.v. infusion over a 2.5-h period beginning 15 min after reperfusion. Neurological status was evaluated daily, and histopathology was quantified at 3 days. Caffeinol therapy significantly improved the neurological score, reduced the total infarct volume (by 52%) and cortical infarct areas at multiple coronal levels, but subcortical infarction and brain swelling were not affected.

Delayed post-ischemic albumin treatment neither improves nor worsens the outcome of transient focal cerebral ischemia in rats.

Human albumin therapy within the first 4 h is highly neuroprotective in focal ischemia, but it is unknown whether delayed albumin therapy is deleterious. Rats received 2 h middle cerebral artery suture-occlusion. Human albumin (25%, 2.5 mg/kg; n=12) or vehicle (0.9% saline, 5 ml/kg; n=9) were administered at 19 h. Neurological status was evaluated daily, and histopathology and brain swelling were quantified at 3 days. Delayed albumin treatment, while ineffective, failed to show adverse effects.

Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia.

Azulenyl nitrones are novel chain-breaking antioxidants with low oxidation potentials and high lipophilicity-properties favoring their efficacy as neuroprotectants. We tested the second-generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation. Neurobehavior was quantified on a standard battery, and brains were perfusion-fixed for quantitative histopathology at 3 days. In 3 independent series, rats were treated at either 2h + 4h, or 2h + 4h + 24h + 48h, after onset of ischemia; vehicle-treated rats received dimethylsulfoxide or saline. All animals (n = 52) developed high-grade neurological deficits (score 11 of 12) during ischemia, which improved, in STAZN-treated rats, within 1-1.5 h of the initial dose and fell to a median score of 3 at 72 h, compared to 8 in vehicle rats. STAZN treatment reduced mean cortical infarct volume by 64-97%, and total infarct volume by 42-72%. In over one-half of STAZN-treated animals, cortical infarction was virtually abolished. Regression analysis predicted that STAZN would confer approximately 50% cortical neuroprotection even in the most severely affected cases. The potency of STAZN was orders-of-magnitude greater than other nitrones such as NXY-059. These results suggest that STAZN has great promise for ischemic stroke.

Experimental intracerebral hemorrhage in the mouse: histological, behavioral, and hemodynamic characterization of a double-injection model.

BACKGROUND AND PURPOSE: A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. METHODS: Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37 degrees C to 37.5 degrees C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-microL injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 microL injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. RESULTS: Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose mean+/-SEM volume was 2.0+/-0.2 mm3 compared with a lesion size of 0.2+/-0.1 mm3 in mice with CSF. Residual swelling of the ipsilateral hemisphere at 48 hours was 5.7% in the hematoma and 1.5% in the CSF groups. Relative CBF in the neocortex ipsilateral to the injection site declined by approximately 45% to 60% during the first 20 minutes after cannula insertion/injection in all groups but began to renormalize at approximately 25 to 30 minutes in the CSF and cannula-only groups; in the hematoma group, cortical hypoperfusion of approximately 35% to 50% persisted during the 90-minute measurement period. CONCLUSIONS: The present ICH model in mice produces a consistent neurological deficit, hypoperfusion, hematoma volume, and brain swelling. This model closely mimics human hypertensive basal ganglionic ICH and should be useful for the evaluation of pharmaceutical therapies. Laser Doppler perfusion imaging is a useful new technique to quantify relative CBF changes and can be used for studies of dynamic changes of CBF in this in vivo model of ICH in mice.

Neuroprotective effect of SolCD39, a novel platelet aggregation inhibitor, on transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: SolCD39 is a soluble form of recombinant human ecto-ATP/ADPase (NTPDase1) and represents a new class of antithrombotic agents. SolCD39 blocks and reverses platelet activation, preventing recruitment of additional platelets into a growing thrombus. The purpose of this study was to examine the effect of solCD39 on neurological deficit, infarct size, and extent of edema after transient middle cerebral artery occlusion (MCAO) in rats. METHODS: Physiologically controlled Sprague-Dawley rats underwent 2-hour MCAO by retrograde insertion of an intraluminal suture coated with poly-l-lysine. The agent (solCD39) was administered intravenously before MCAO or at 1-hour or 3-hour recirculation. Other groups received vehicle (Tris-buffered saline) or human albumin (as a "positive" neuroprotective control; 25%, 0.5% of body weight) at 1-hour recirculation. Neurological status was evaluated during occlusion (at 60 minutes) and daily for 3 days after MCAO. Brains were perfusion-fixed at 72 hours, and infarct volumes and brain swelling were determined. RESULTS: Pretreatment with solCD39 significantly improved the neurological score at 72 hours compared with the vehicle group (4.4+/-0.6 versus 7.6+/-0.6, respectively; P=0.008). Cortical infarct areas were significantly reduced at multiple levels by pretreatment with solCD39. Total striatal infarct area was also significantly reduced compared with vehicle by both solCD39 pretreatment (48% mean reduction) and solCD39 treatment at 3-hour recirculation (51% mean reduction). Treatment with SolCD39 significantly reduced total infarct volume (corrected for brain swelling) by an average of 71% to 72% when administered either before ischemia or at 3 hours of recirculation compared with vehicle. Treatment with albumin significantly reduced neurological score and total, cortical, and subcortical infarction at multiple levels, as expected. CONCLUSIONS: Treatment with SolCD39, administered either before or at 3 hours after MCAO, improves neurological score and reduces infarct size compared with vehicle. A pharmacological agent of this type appears to have potential for the treatment of focal ischemic stroke.

Enriched environment delays the onset of hippocampal damage after global cerebral ischemia in rats.

An enriched environment has been shown to improve cognitive, behavioral and histopathological outcome after focal cerebral ischemia and head trauma. The purpose of this study was to determine the effect of an enriched environment on histopathology following global cerebral ischemia. Wistar rats (21 weeks of age) were placed in different environments [standard cages (SC) or enriched environment (EE) cages] for 2 months before and either 6 days or 2 months after ischemia. Rats underwent 10 min of global ischemia by bilateral carotid artery occlusions plus hypotension. Five groups (n=4-5 in each group) were studied: (1) rats kept in SC before and 2 months after ischemia; (2) rats kept in SC before ischemia but transferred to an EE for 2 months after ischemia; (3) rats kept in EE before and after ischemia for 2 months; (4) rats kept in SC before and 6 days after ischemia; (5) rats kept in EE before and 6 days after ischemia. At 7 days or 2 months after ischemia, brains were perfusion-fixed, and ischemic injury was assessed by counting numbers of normal neurons in the hippocampal CA1 sector. Physiological variables showed no inter-group differences. Rats housed in EE for 2 months before and for 6 days (but not 2 months) after global ischemia showed significantly better preservation of pyramidal neurons in the hippocampal CA1 area when compared to control animals (middle CA1, 20.5+/-5.4 vs. 2.8+/-0.6; lateral CA1, 31.5+/-7.2 vs. 2.6+/-0.6, respectively). The present data suggest that housing in EE for 2 months before and 6 days after ischemia can delay the onset of damage to hippocampal pyramidal neurons, which eventually occurs despite 2-month EE.