Isaac E Silverman

Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke Results of the MERCI Trial

Background and Purpose— The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods— We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results— Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Conclusions— A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology.

Objectives: 1) To evaluate the risk of subsequent stroke or death in patients with a cryptogenic stroke and a patent foramen ovale (PFO), atrial septal aneurysm (ASA), or both. 2) To establish the optimal method of stroke prevention in this population of patients. Methods: MEDLINE, the Cochrane database of systematic reviews, key meeting abstracts from 1997 to 2002, and relevant reference lists were searched to select studies that prospectively collected outcome data in cryptogenic stroke patients with and without interatrial septal abnormalities. Studies were also selected that prospectively compared at least two treatment options. The quality of each study was graded (class I to IV) using a standard classification-of-evidence scheme for each question. Risk analyses were performed and data were pooled when appropriate. Results: The literature search generated 129 articles of which only four fulfilled the inclusion and exclusion criteria. Two studies were graded class I, one study was graded class II, and one study was graded class IV for prognosis. Pooled results of the two class I and one class II studies demonstrated no increased risk of subsequent stroke or death in patients with PFO compared to those without (RR = 0.95, 95% CI 0.62 to 1.44). One class I study found increased risk of recurrent stroke in patients with PFO and ASA (annual rate = 3.8% versus 1.05%, RR = 2.98, 95% CI 1.17 to 7.58) but not increased risk of a composite of stroke and death (annual rate = 3.8% versus 1.8%, RR = 2.10, 95% CI 0.86 to 5.06). Regarding therapy, one study was graded class II, one study class III, and two studies class IV. Among patients with cryptogenic stroke and PFO or ASA, there was no significant difference in stroke or death rate in warfarin-treated patients relative to aspirin-treated patients and the confidence intervals were unable to rule out a benefit of one drug over the other (annual rate = 4.7% versus 8.9%, RR = 0.53, 95% CI 0.18 to 1.58). Minor bleeding rates were higher in the cohort of patients who received warfarin (22.9/100 patient-years versus 8.66/100 patient-years, rate ratio = 2.64, p < 0.001). No studies compared medical therapy with surgical or endovascular closure. Conclusion: PFO is not associated with increased risk of subsequent stroke or death among medically treated patients with cryptogenic stroke. However, both PFO and ASA possibly increase the risk of subsequent stroke (but not death) in medically treated patients younger than 55 years. In patients with a cryptogenic stroke and an atrial septal abnormality the evidence is insufficient to determine if warfarin or aspirin is superior in preventing recurrent stroke or death, but minor bleeding is more frequent with warfarin. There is insufficient evidence to evaluate the efficacy of surgical or endovascular closure.Objectives1) To evaluate the risk of subsequent stroke or death in patients with a cryptogenic stroke and a patent foramen ovale (PFO), atrial septal aneurysm (ASA), or both. 2) To establish the optimal method of stroke prevention in this population of patients. MethodsMEDLINE, the Cochrane database of systematic reviews, key meeting abstracts from 1997 to 2002, and relevant reference lists were searched to select studies that prospectively collected outcome data in cryptogenic stroke patients with and without interatrial septal abnormalities. Studies were also selected that prospectively compared at least two treatment options. The quality of each study was graded (class I to IV) using a standard classification-of-evidence scheme for each question. Risk analyses were performed and data were pooled when appropriate. ResultsThe literature search generated 129 articles of which only four fulfilled the inclusion and exclusion criteria. Two studies were graded class I, one study was graded class II, and one study was graded class IV for prognosis. Pooled results of the two class I and one class II studies demonstrated no increased risk of subsequent stroke or death in patients with PFO compared to those without (RR = 0.95, 95% CI 0.62 to 1.44). One class I study found increased risk of recurrent stroke in patients with PFO and ASA (annual rate = 3.8% versus 1.05%, RR = 2.98, 95% CI 1.17 to 7.58) but not increased risk of a composite of stroke and death (annual rate = 3.8% versus 1.8%, RR = 2.10, 95% CI 0.86 to 5.06). Regarding therapy, one study was graded class II, one study class III, and two studies class IV. Among patients with cryptogenic stroke and PFO or ASA, there was no significant difference in stroke or death rate in warfarin-treated patients relative to aspirin-treated patients and the confidence intervals were unable to rule out a benefit of one drug over the other (annual rate = 4.7% versus 8.9%, RR = 0.53, 95% CI 0.18 to 1.58). Minor bleeding rates were higher in the cohort of patients who received warfarin (22.9/100 patient-years versus 8.66/100 patient-years, rate ratio = 2.64, p < 0.001). No studies compared medical therapy with surgical or endovascular closure. ConclusionPFO is not associated with increased risk of subsequent stroke or death among medically treated patients with cryptogenic stroke. However, both PFO and ASA possibly increase the risk of subsequent stroke (but not death) in medically treated patients younger than 55 years. In patients with a cryptogenic stroke and an atrial septal abnormality the evidence is insufficient to determine if warfarin or aspirin is superior in preventing recurrent stroke or death, but minor bleeding is more frequent with warfarin. There is insufficient evidence to evaluate the efficacy of surgical or endovascular closure.

Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence

BACKGROUND Acute ischemic strokes are associated with poor outcomes and high health care burden. Evidence exists evaluating the use of neurothrombectomy devices in patients receiving currently recommended treatments that may have limited efficacy. PURPOSE To describe the state of the evidence supporting use of neurothrombectomy devices in the treatment of acute ischemic stroke. DATA SOURCES MEDLINE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Web of Science were searched, without language restrictions, from their inception through May 2010. The MEDLINE and Cochrane Central Register of Controlled Trials searches were updated through November 2010. STUDY SELECTION Two independent investigators screened citations for human studies of any design or case series or case reports of patients with an acute ischemic stroke that evaluated a neurothrombectomy device and reported at least 1 clinical effectiveness outcome or harm. DATA EXTRACTION Using standardized protocols, 2 independent investigators extracted information about study characteristics and outcomes, and a third reviewer resolved disagreement. DATA SYNTHESIS 87 articles met eligibility criteria, including 18 prospective single-group studies, 7 noncomparative retrospective studies, and 62 case series or case reports. Two U.S. Food and Drug Administration (FDA)-cleared devices, the MERCI Retriever (Concentric Medical, Mountain View, California) (40%) and the Penumbra System (Penumbra, Alameda, California) (9%), represented a large portion of the available data. All prospective and retrospective studies provided data on successful recanalization with widely varying rates (43% to 78% with the MERCI Retriever and 83% to 100% with the Penumbra System). Rates of harms, including symptomatic (16 studies; 0% to 10% with the MERCI Retriever and 0% to 11% with the Penumbra System) or asymptomatic (13 studies; 28% to 43% and 1% to 30%, respectively) intracranial hemorrhage and vessel perforation or dissection (11 studies; 0% to 7% and 0% to 5%, respectively), also varied by device. Predictors of harm included older age, history of stroke, and higher baseline stroke severity scores, whereas successful recanalization was the sole predictor of good outcomes. LIMITATIONS Most available data are from single-group, noncomparative studies. In addition, the patient population most likely to benefit from these devices is undetermined. CONCLUSION Currently available neurothrombectomy devices offer intriguing treatment options in patients with acute ischemic stroke. Future trials should use a randomized design, with adequate power to show equivalency or noninferiority between competing strategies or devices, and strive to identify populations that are most likely to benefit from use of neurothrombectomy devices. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Acute Stroke Management in the Elderly

Background and Purpose: Though the proportion of elderly stroke patients is increasing, patients >80 years are often excluded from clinical stroke trials. We reviewed the management of older patients presenting with acute ischemic stroke (AIS) and assessed the safety and efficacy of recombinant tissue plasminogen activator (rtPA) administration in a community-based setting. Methods: A retrospective review of patients >80 years (n = 341) admitted to a community stroke center with AIS were compared to their younger counterparts (n = 690) using the stroke center database from April 2003 to December 2005. Parameters that were measured included admission and discharge NIH Stroke Scale (NIHSS), rate of thrombolytic treatment, the frequency and etiology of thrombolytic exclusion criteria and complications from rtPA for the different aged populations. Additional data were collected for Barthel Index at 12 months. Results: A total of 166 patients underwent thrombolysis. Older patients were not delayed in reaching the hospital within 3 h of stroke onset (182/690, 26%, in the <80 cohort vs. 98/341, 29%, in the ≧80 cohort). Although the overall rates of tPA use were similar in both the young and aged cohort, older patients were less likely to be treated with rtPA because of reasons not listed as exclusion criteria (17% in the <80 cohort vs. 32% in the ≧80 cohort).The older group did not have an excess risk of intracranial hemorrhage following rtPA infusion despite equivalent NIHSS on admission (13.5 in the <80 cohort vs. 12.4 in the ≧80 cohort). Both groups showed improvement in NIHSS following thrombolytic treatment with a drop of 7.7 points in the younger age group and 5.6 points in the older group. Elderly patients treated with rtPA had a comparable 12-month modified Barthel Index score to younger cohorts. Conclusions: Early treatment with rtPA in patients >80 years appears to be both safe and efficacious. Treated patients showed improvements both acutely (a decrease in NIHSS at 72 h) and chronically, as shown by a sustained improvement in the Barthel Index. A large number of elderly patients were excluded from rtPA treatment despite arriving within the time frame of treatment for reasons not considered as traditional exclusion criteria. Older patients with AIS can be treated safely with thrombolytic therapy in a community setting. This therapy should not be withheld on the basis of age.

Determinants and clinical significance of persistent residual shunting in patients with percutaneous patent foramen ovale closure devices

BACKGROUND Percutaneous patent foramen closure has emerged as a dynamic therapy for stroke prevention secondary to paradoxical embolism. Recent reports, however, have documented uncertain clinical efficacy and patients with incomplete PFO closure may remain at risk of recurrent events. We sought to identify echocardiographic determinants and the clinical significance of persistent residual shunting after percutaneous PFO closure. METHODS From 2002 to 2008, 51 consecutive patients with recurrent stroke (n=46) or transient ischemic attack (TIA) (n=5) underwent percutaneous PFO closure at a tertiary care hospital. PFO size, degree of shunt, tunnel length, and atrial septal aneurysm geometry were documented at the time of device implantation. All patients received follow-up with transesophageal (n=43) or transthoracic (n=8) echocardiography 6.7+/-2 months post procedure and presence of residual shunting and recurrent stroke/TIA were recorded. RESULTS All patients underwent percutaneous PFO closure without complication. Ten patients (20%) demonstrated residual right-to-left shunting at the time of follow-up: color Doppler (2), mild (n=3), moderate (n=2) and severe (n=3). Univariate analysis revealed larger PFO size (F=4.71, p=0.036) as the only independent predictor of residual shunting after PFO closure. Ninety six percent of patients remained stroke and TIA free 3 years+/-8 months post closure, with no clinical differences between the two groups. CONCLUSIONS In patients undergoing percutaneous PFO closure for stroke or TIA, a larger PFO size predisposes to residual shunting approximately 6 months post PFO closure, but with no short term increased risk of recurrent thromboembolic events.

Cerebral Edema During Treatment of Diabetic Ketoacidosis in an Adult With New Onset Diabetes

Introduction: Diabetic ketoacidosis (DKA) continues to be a medical emergency, in part because of a rare and devastating complication associated with its treatment, cerebral edema. In children, cerebral edema is the principal cause of mortality, but clinically significant cerebral edema in adults is rare.Methods and Results: We report the case of a 27-year-old male (not previously known to be diabetic) who presented with a first episode of DKA complicated by the development of fatal cerebral edema despite medical treatment.Conclusion: The pathophysiological mechanisms for cerebral edema associated with DKA occuring in children and adults are believed to be similar and are discussed in this report. However, patients who develop cerebral edema may deteriorate rapidly, and experience with successful treatment has been limited.

Rheumatoid Meningitis Presenting With Multiple Strokelike Episodes

Discussion | Greco et al6 described the presence of inclusions in 11 cases of men with FXTAS aged 67 to 87 years. In our patient, the number of inclusions were in the low range when compared with those cases. In summary, FXTAS is thought to be a disorder of aging in carriers of FMR1 premutation; however, this case documents that FXTAS can occur earlier in adult life, particularly if another disease process is occurring, such as substance abuse, that may exacerbate the pathological process of FXTAS.5