Meschia, James F.

Background and Purpose— The Carotid Revascularization Endarterectomy Versus Stenting Trial was completed with a low stroke and death rate. A lead-in series of patients receiving carotid artery stenting was used to select the physician-operators for the study, where performance was evaluated by complication rates and by peer review of cases. Herein, we assess the potential contribution of statistical evaluation of complication rates. Methods— The ability to discriminate between stent operators who can successfully meet the published guideline of <3% combined rate of stroke and death is calculated under the binomial distribution, based on a small consecutive case series (n=24 patients). Results— A criterion of ≤2 stroke or death events among the 24 patients (<8% event rate) was required of operators. Setting such a high criterion, however, ensures an inability to exclude operators who cannot meet the criteria. In fact, if a good operator is defined as having a 2% event rate and a poor operator as a 6% event rate, even a series of 240 patients would (on average) still exclude 5.4% of the good operators and include 4.6% of the poor operators. Conclusions— The low periprocedural event rates in the trial suggest success in separating skillful operators from less skillful. However, it seems unlikely that statistical assessment of event rates in the lead-in contributed to successful selection, but rather successful selection was more likely because of peer review of subjective and other factors including patient volume and technical approaches. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00004732.

Stroke remains an exceedingly incident and prevalent public health burden across the globe, with an estimated 16 million new strokes per annum and prevalence over 60 million, and extracranial internal carotid artery atherosclerotic disease is an important risk factor for stroke. Randomized trials of surgical treatment were conducted (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial) and demonstrated efficacy of carotid endarterectomy for secondary prevention of stroke in patients with cerebrovascular events (e.g. ipsilateral stroke, transient ischemic attack, and/or amaurosis fugax) attributable to a diseased artery with 50–99% stenosis. Therapeutic clarity, however, proved elusive with asymptomatic carotid artery disease. Asymptomatic Carotid Atherosclerosis Study (ACAS), Asymptomatic Carotid Surgery Trial, and Veterans Affairs Cooperative Study (VACS) suggested only modest benefit from surgical intervention for primary stroke prevention and the best medical therapy at the time of these trials is not comparable to modern medical therapy. ACT-1, Asymptomatic Carotid Surgery Trial-2, Stent-Protected Angioplasty in asymptomatic Carotid artery stenosis versus Endarterectomy Trial-2, European Carotid Surgery Trial-2, Carotid Revascularization Endarterectomy Versus Stenting Trial-2 are trials that are recent, ongoing, or in development that include diverse populations across Europe and North America, complementary trial designs, and a collaborative spirit that should provide clinicians with evidence that informs best clinical practice for asymptomatic carotid artery disease.

Background and Purpose— Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods— The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research–generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions— The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.

Background Acetazolamide induces cerebral vasodilatation and may be used to measure cerebrovascular reserve in patients with cerebral arteriopathy. While acetazolamide is known to induce transient neurologic deficits as a result of “steal phenomenon,” prolonged deficits have rarely been described. Methods Retrospective, single-centre case review from 2011 to 2012. Results We describe 3 patients ages 41, 60 and 65 years (2 women; 1 man) who developed prolonged neurological deterioration following administration of acetazolamide in the acute phase following presentation for evaluation of cerebrovascular reserve. Two patients presented with hemispheric ischaemic symptoms; one presented with headache and parietal convexity subarachnoid haemorrhage. One patient had extensive intracranial vascular disease consistent with a moyamoya-like syndrome with left middle cerebral artery (MCA) occlusion and severe left supraclinoid internal carotid artery (ICA) stenosis. Another had 50% left MCA stenosis as well as > 70% stenosis of the left ICA. She failed medical therapy, L CAS, L MCA angioplasty, and left EC-IC bypass. A third patient had occlusion of the right ICA and severe left ICA stenosis. In every case, acetazolamide challenge was carried out in the acute phase following presentation. All three patients developed significant prolonged worsening of neurologic deficits following the administration of acetazolamide (1 g). Patients received aggressive intravenous hydration. Two of the patients regained pre-acetazolamide neurological status within 18 hours. The third patient recovered several days after emergency left carotid artery stenting. Imaging studies (CT in 2 cases; MRI in 1) did not reveal interval haemorrhage or additional ischaemic changes in any case. Conclusion Administration of acetazolamide has the potential to induce decline in neurological function after administration in the acute phase and may be persistent for several hours or days. A steal phenomenon is a possible mechanism. The combination of severe extracranial and intracranial vascular disease may predispose to prolonged deficits and may be a contraindication to diagnostic use of acetazolamide. Disclosures R. Tawk: None. B. Eidelman: None. R. Hanel: None. J. Meschia: None. K. Barrett: None.

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Objective: To expand the adverse events associated with metronidazole to include nonconvulsive status epilepticus (NCSE). Design: Observational single case report of a rare association. Setting: Hospitalized lung transplant recipient treated with metronidazole for prevention of infection. Patient: A 56-year-old man with systemic symptoms, peripheral neuropathy, generalized seizure, and a subsequent acute deterioration of mental status due to NCSE. Interventions: Administration of midazolam was successful in terminating status epilepticus. Main Outcome Measures: Abrupt termination of NCSE was evident on continuous bedside electroencephalogam associated with clinical resolution of mental status. Results: Recovery occurred from NCSE eventually deteriorating to a fatal outcome. Conclusions: Metronidazole may be associated with successfully treated NCSE.

Background— Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods and Results— CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63–4.76). Conclusions— Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00004732.