Rakesh Khatri

Blood–brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke

It has been more than a century since Paul Ehrlich, in 1885, and later his student Edwin Goldmann, proposed that a barrier existed between the CNS and the peripheral circulation.1 While studying the limited permeation of potassium ferrocyanate into the brain in 1900, Lewandowsky coined the term bluthirnschranke, blood–brain barrier (BBB).1 The BBB is considered the gatekeeper of the CNS, whose main role is to maintain the fragile homeostasis of the brain designed by segregating the CNS from the systemic circulation. The BBB is composed of endothelial cells, pericytes, astrocytes, neurons, and the extracellular matrix (ECM), which are collectively known as the neurovascular unit (NVU). BBB endothelial cells lack fenestrations, have tight junctions (TJs), have minimal pinocytotic activity, and express a number of enzymes capable of degrading both harmful and therapeutic molecules. They also have increased mitochondrial content, which is required for the multiple energy-dependent processes involved in nutrient support and protection of the brain.1,–,3 Pericytes are vascular smooth-muscle-lineage cells that occur as solitary cells embedded in the basement membrane of microvessels and have their own characteristic morphology.4 Both the endothelial cells and pericytes are surrounded by the basal lamina, which is 30- to 40-nm contiguous with the plasma membranes of astrocyte end-feet. The basal lamina supports and anchors cells via adhesion receptors and regulates intercellular communication. Astrocytes play a very important role not only in BBB support and its maintenance but also in neuron–NVU interactions. Under conditions of ischemia, there is a disruption of the bidirectional communication between microvessels and neurons with the participation of the intervening astrocytes.3 The greater the distance between the microvessels and the neurons [(m − n) distance], the higher the likelihood of being prone to ischemic injury.3 Microglial cells are basically the macrophages of …

Microcatheter to Recanalization (Procedure Time) Predicts Outcomes in Endovascular Treatment in Patients with Acute Ischemic Stroke: When Do We Stop?

This study addresses the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. Demographics, NIHSS scores before and 1 day after the procedure, and modified Rankin Scale scores were assessed in 209 patients. Patients with procedure times ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure times ≥30 minutes. Rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment. Unfavorable outcome was positively associated with age, admission NIHSS strata, and longer procedure times. BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke consists of various mechanical and pharmacologic modalities used for recanalization of arterial occlusions. We performed this study to determine the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. MATERIALS AND METHODS: We analyzed data from consecutive patients with acute ischemic stroke who underwent endovascular treatment during a 6-year period. Demographic characteristics, NIHSS score before and 24 hours after the procedure, and discharge mRS score were ascertained. Procedure time was defined by the time interval between microcatheter placement and recanalization or completion of the procedure. We estimated the procedure time after which favorable clinical outcome was unlikely, even after adjustment for age, time from symptom onset, and admission NIHSS scores. RESULTS: We analyzed 209 patients undergoing endovascular treatment (mean age, 65 ± 16 years; 109 [52%] men; mean admission/preprocedural NIHSS score, 15.3 ± 6.8). Complete or partial recanalization was observed in 176 (84.2%) patients, while unfavorable outcome (mRS 3–6) was observed in 138 (66%) patients at discharge. In univariate analysis, patients with procedure time ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure time ≥30 minutes (52.3% versus 72.2%, P = .0049). In our analysis, the rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment in the Prourokinase for Acute Ischemic Stroke Trial. In logistic regression analysis, unfavorable outcome was positively associated with age (P = .0012), admission NIHSS strata (P = .0017), and longer procedure times (P = .0379). CONCLUSIONS: Procedure time in patients with acute ischemic stroke appears to be a critical determinant of outcomes following endovascular treatment. This highlights the need for procedure time guidelines for patients being considered for endovascular treatment in acute ischemic stroke.

Age differential between outcomes of carotid angioplasty and stent placement and carotid endarterectomy in general practice

BACKGROUND Data derived from prospective randomized clinical trials suggest differential comparative benefit between carotid angioplasty and stent (CAS) placement and carotid endarterectomy (CEA) in various age strata. We sought to investigate the impact of age on outcomes of CAS and CEA in general practice. METHODS We analyzed the data from the Nationwide Inpatient Sample (NIS), which is representative of all admissions in the United States from 2005 to 2008. The primary end point was occurrence of stroke, cardiac complications, or death during the postprocedural period. Outcomes of interest were compared between patients aged ≥70 years and <70 years, undergoing CEA and CAS. Multivariate logistic regression was performed to determine the effect of age on occurrence of postoperative stroke, cardiac complications, or death. Covariates included in the logistic regression were patients age, gender, comorbid conditions, including hypertension, diabetes mellitus (DM), chronic lung disease, coronary artery disease (CAD), congestive heart failure (CHF), and renal failure; symptom status (symptomatic vs asymptomatic status), and hospital characteristics. RESULTS Of the total 495,331 estimated patients who received treatment for CAD during the study period, 88% underwent CEA and the remaining 12% underwent CAS. Of the total procedures, 41% of the procedures were performed in patients aged <70 years compared to the remaining 59% that were performed among patients aged ≥70 years. For patients undergoing CAS, age ≥70 years was an important predictor of postoperative stroke (P = .0025; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.5) and cardiac complications postprocedure (P = .045; OR, 1.3; 95% CI, 1.0-1.6). For patients undergoing CEA, age ≥70 years was associated with higher cardiac complications (P < .001; OR, 1.5; 95% CI, 1.3-1.7) and higher postoperative mortality risk (P = .0008; OR, 1.4; 95% CI, 1.1-1.8) compared to patients aged <70 years. The increased risk of composite end point (postoperative stroke/cardiac complications/mortality) among patients aged ≥70 years was a significant factor for patients undergoing either CAS or CEA (OR of 1.3 for both procedures). CONCLUSION Our analysis suggests that most CAS and CEAs are performed in patients aged ≥70 years in general practice, and higher rates of postoperative complications are observed among these patients regardless of procedure choice.

A comparison of outcomes associated with carotid artery stent placement performed within and outside clinical trials in the United States

BACKGROUND A discrepancy between characteristics of patients treated with carotid angioplasty and stent placement (CAS) within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may limit generalization of clinical trial results. The objective of this study was to identify differences in demographic and clinical characteristics and outcomes related to CAS in patients treated within clinical trials and those treated outside clinical trials in a large national cohort. METHODS We determined the frequency of CAS performed within and outside clinical trials and associated in-hospital outcomes using data from the Nationwide Inpatient Survey data files from 2005 to 2009. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. RESULTS Of the 81,638 patients who underwent CAS, 16,078 (19.6%) underwent the procedure as part of a clinical trial. The mean age of the patients was significantly lower in patients treated with CAS as part of a clinical trial than those treated with CAS outside a clinical trial. The proportion of women and nonwhites was lower among patients treated with CAS as part of a clinical trial. The in-hospital mortality was two-fold higher among patients treated with CAS outside clinical trials (1.12% vs 0.53%; P = .0005). The rate of composite endpoint of stroke, cardiac events, and death was significantly higher among patients treated with CAS outside clinical trials (P = .02). After adjusting for age, gender, presence of renal failure, and hospital bed size, CAS performed as part of a clinical trial was associated with lower rates of in-hospital mortality (odds ratio, 0.467; 95% confidence interval, 0.290-0.751; P = .0017) and composite endpoint of stroke, cardiac events, and death (odds ratio, 0.752; 95% confidence interval, 0.594-0.952; P = .0180). CONCLUSIONS Our results suggest that CAS procedures performed as part of clinical trials was associated with lower rates of in-hospital mortality and composite endpoint of stroke, cardiac events, and death in United States. These findings highlight the need for strategies that ensure appropriate adoption of CAS to ensure that the benefits observed in clinical trials can be replicated in general practice.

Rate of postprocedural stroke and death in SAMMPRIS trial-eligible patients treated with intracranial angioplasty and/or stent placement in practice.

BACKGROUND The SAMMPRIS (Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial, comparing aggressive medical vs stent treatment in patients with symptomatic intracranial stenosis, was halted after a 14% stroke and death rate was observed in the stent-treated group. OBJECTIVE To study the 30-day stroke and death rate in intracranial angioplasty- and stent-treated patients meeting SAMMPRIS trial eligibility criteria. METHODS A retrospective analysis of 96 patients treated with intracranial angioplasty and stent placement at 3 university-affiliated institutions was performed. Patients were divided into SAMMPRIS trial eligible and ineligible groups based on inclusion and exclusion criteria for the SAMMPRIS trial. RESULTS Sixty-nine patients were determined to be SAMMPRIS eligible and 27 patients were ineligible. The SAMMPRIS-eligible group was divided into angioplasty- and stent-treated subgroups (30 and 39 patients, respectively). The overall 30-day postprocedure stroke and death rate was 7.2% in the SAMMPRIS-eligible group and 7.4% in the SAMMPRIS-ineligible group (P = .97). The 30-day postprocedure stroke and death rate was 3.3% in the SAMMPRIS-eligible, angioplasty-treated subgroup and 10.2% in the SAMMPRIS-eligible, stent-treated subgroup (P = .27). CONCLUSION The overall 30-day postprocedure stroke and death rate in our study was lower in both SAMMPRIS-eligible and -ineligible groups than the reported 14% stroke and death rate in the SAMMPRIS trial. We hypothesize that a more judicious use of primary angioplasty may be responsible for better postprocedure outcomes and should be considered an acceptable treatment in future trials.

Frequency and factors associated with unsuccessful lead (first) coil placement in patients undergoing coil embolization of intracranial aneurysms.

BACKGROUND There is limited knowledge about associated rates, aneurysm characteristics, technical factors, and immediate impact of unsuccessful placement of the lead (first) coil during endovascular embolization of intracranial aneurysms. OBJECTIVE To determine the rates, associated risk factors, and consequences of lead coil placement failure in consecutive embolization procedures. METHODS We reviewed clinical and procedural aspects of all endovascular coil embolizations performed at our 2 academic centers over a period of 3.5 years (2006-2010). Morphologic characteristics of the aneurysm and technical aspects of the treatment were recorded. We also performed a flow model analysis to assess the relationship between aneurysm dimensions, length of coil, packing density with first coil, and occurrence of lead coil placement failure. RESULTS There were 24 (14%) lead coil placement failure procedures in 172 aneurysm embolization procedures; in 23 of 24 (96%) patients with lead coil placement failure, the failure occurred in aneurysms less than 10 mm in size. The main technical factors associated with lead coil placement failure were related to the coil (length, diameter, and type) followed by microcatheter support failure. Among these patients, 21 (87.5%) required change in the coil length, 17 (70.8%) change in coil diameter, and 10 (41.7%) change in coil type (brand and/or configuration) for successful placement of the lead coil. A total of 4 (16.7%) patients required change in microcatheter, and 6 (24.9%) patients had balloon/stent assistance for successful lead coil placement. Two of 24 (8.3%) patients had rupture of their aneurysms during the attempt to reposition the lead coil. In our flow model, these clinical observations were reproduced with higher risk of lead coil failure in smaller aneurysms. CONCLUSION Lead coil placement failure is not infrequent during embolization of intracranial aneurysms and may increase the risk of complications. Appropriate coil selection, particularly coil length in small aneurysms, may reduce the rate of lead coil placement failure and associated complications.

Combination of noninvasive neurovascular imaging modalities in stroke patients: patterns of use and impact on need for digital subtraction angiography.

BACKGROUND The diagnostic work-up of acute stroke relies on the use of proper imaging studies. We sought to determine the use of a combination of 2 noninvasive tests, namely magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) in diagnosing vascular lesions and the necessity for a subsequent digital subtraction angiography (DSA) for the definitive diagnosis. METHODS Patients admitted to 2 comprehensive stroke centers between January 2008 and July 2010 who had an equivocal initial noninvasive test were reviewed. The proportions of patients who underwent CTA and MRA in combination and those who required additional DSA for definitive diagnosis were determined. The diagnostic yield and impact on management in patients with CTA and MRA combination was compared with patients who underwent CTA and MRA followed by DSA. RESULTS Among a total of 1063 patients (mean age ± SD 63 ± 16), 384 (36%) underwent >1 vascular imaging study. There was no difference in the rates of cardiovascular risk factors and stroke subtype between different combination groups. The agreement between CTA and MRA was high (concordance 81%). Among the 164 patients who underwent both CTA and MRA, a DSA was required for resolution/confirmation in only 27 (16%) patients. Among these 27, DSA findings changed the clinical decision-making in 22 (82%) patients (11 stenotic severities and 11 diagnoses of arteriovenous fistula, aneurysm, or dissection). CONCLUSIONS In our experience, a combination of CTA and MRA was frequently used in patients in whom the initial noninvasive imaging was determined insufficient. The combination of findings from CTA and MRA were considered adequate in a large portion of patients resulting in a lower requirement for DSA and higher treatment impact from DSA.

Occurrence and Prognostic Significance of Cervical Pseudodissection Phenomenon Associated with Acute Intracranial Internal Carotid Artery Occlusion

Acute stroke from intracranial internal carotid artery (ICA) occlusion can occasionally resemble angiographic cervical ICA dissection which may cause delays in endovascular acute ischemic stroke treatment.

The use of vascular closure devices outside the catheterization laboratory after neurointerventional procedures is safe and effective: Evidence from a retrospective study

Purpose To investigate the feasibility and safety of vascular closure device (VCD) deployment outside the catheterization laboratory. Methods Medical records were reviewed of all 799 patients (396 men; mean age 56±16 years) who underwent deployment of 918 VCDs following diagnostic or therapeutic neurointerventional procedures over a 2-year period at 2 comprehensive stroke centers. The rates of major vascular complications in patients undergoing VCD deployment in and outside the catheterization laboratory were compared. Major vascular complications were adjudicated using definitions by the Society of Interventional Radiology; comparisons were made between different procedure types and closure devices. Results During the observation period, 103 (11.2%) of 918 VCD deployments were performed outside the catheterization laboratory. Age, gender, procedure type, and device types were not different between the groups. A total of 10 (1.1%) major vascular complications occurred, including dissection requiring angioplasty (n=1), hematoma requiring blood transfusion (n=4), pseudoaneurysm requiring thrombin injection (n=2), and lower limb ischemia necessitating surgical removal of the VCD (n=3). Rates of major vascular complications were not significantly different between VCDs deployed inside the catheterization laboratory [1.0% (8/815)] compared to outside [1.9% (2/103), p=0.3]. Conclusion VCD deployment outside the catheterization laboratory does not increase the rate of major vascular complications and may be an alternative approach for femoral artery hemostasis when VCD deployment needs to be deferred.

Early migration of a self-expanding intracranial stent after the treatment of a basilar trunk aneurysm: report of a second case.

administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97(4):771-778. 2. Starke RM, Kim GH, Fernandez A, et al. Impact of a protocol for acute antifibrinolytic therapy on aneurysm rebleeding after subarachnoid hemorrhage. Stroke. 2008;39(9):2617-2621. 3. Harrigan MR, Ardelt AA. In Reply: Short term antifibrinolytic therapy prior to early aneurysm treatment in subarachnoid hemorrhage: Effects on rehemorrhage, cerebral ischemia, and hydrocephalus. Neurosurgery. 2011 Mar 8 [Epub ahead of print]. 4. Harrigan MR, Rajneesh KF, Ardelt AA, Fisher WS III. Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. Neurosurgery. 2010;67(4): 935-939; discussion 939-940.