Thrombolysis in Stroke Despite Contraindications or Warnings?
In this edition of Stroke, Frank and colleagues investigated the outcome of acute stroke patients that received intravenous tissue plasminogen activator (tPA), despite having cited (relative) contraindications. Patient data were obtained from the Virtual International Stroke Trials Archives (VISTA), which is comprised of patients included in neuroprotectant trials from 1998 to 2008, and for which the decision to give tPA was reached independently from the original trial inclusion and exclusion criteria. Patients from trials that had tested effects of thrombolysis or drugs known to influence poststroke outcome or patients lacking relevant baseline or outcome information were excluded. All in all, data from 9613 (8438) patients presenting within 12 (3) hours of symptom onset were collected. Of these, 2755 (32.6%) were thrombolysed. Thrombolysed patients were younger, had more severe deficits, and less frequently stroke risk factors then nonthrombolysed patients. The primary outcome was the modified Rankin Score (mRS) distribution at 90 days. Information on symptomatic intracranial hemorrhage (SICH) was available for 7326 patients. Almost half of all thrombolysed patients (49.6%) had at least 1 contraindication to tPA. Despite this, most patient subgroups (as stratified by their respective contraindication) seemed to benefit from treatment, or at least were not significantly harmed with the exception of patients that were on dual antiplatelet therapy. This subgroup had a tendency toward worse outcomes possibly related to the high SICH rate (not significant). Do these results indicate that (relative) contraindications can always be ignored? Hardly! However, this study indicates that treating (stroke) physicians are more often right than wrong in treating patients with contraindications, and highlights the importance of judging tPA eligibility based on the entire circumstances rather than a single point on a checklist. See p 727.
Early MRI in TIA and Minor Stroke: Do it or Lose it
MRI is a valuable tool for stroke diagnosis and outcome prediction. However, after minor strokes or in patients with transient ischemic attacks (TIA), substantial temporal variability in lesion evolution have been observed, which can range from clear infarction to complete lesion reversal. Moreau and colleagues investigated the impact of late (90-day) versus early MRI on the ability to visualize ischemic lesions after minor stroke (National Institute of Health Stroke Scale [NIHSS] <4 or TIA; symptoms lasting ≥5 minutes, 52%) in 263 prospectively enrolled adult patients. Patients that received thrombolytic therapy were excluded. Patients underwent 3T MRI (including diffusion weighted imaging [DWI], fluid attenuated inversion recovery, and T2) at baseline and 90-day follow-up. Raters interpreted the 90-day MRI with knowledge of clinical data to rate stroke presence, and whether it was related to the original symptoms. Then, the baseline MRI was interpreted accordingly. Lesions were rated as acute, subacute, or chronic. In 56% of cases, the 90-day MRI showed a stroke of any age compared with 68% of the baseline MRIs. Of the patients with negative 90-day scan, 30% had a clearly identifiable lesion as defined by prior acute or subacute DWI. Expectedly, false-negative 90-day MRI were more frequent in TIA patients (P=0.008) versus patients with minor stroke (P=0.05). Conversely, on 17% (n=46) of 90-day MRI, a stroke was noted that was not visualized on the baseline scan, 80% of which were clinically silent. However, 26 of these 46 lesions could only be identified as a new stroke by comparison with the baseline scan. Of note, in 19 patients with repeat MRA, recanalization of the originally occluded artery had occurred in 95% of cases by 90 days. Although this study does not inform on the optimal time window for using 3T MRI, it does highlight that delayed imaging at 90 days in patients with prior minor or transient symptoms can be falsely reassuring in a significant number of patients. Accordingly, a high-index suspicion for an ischemic event should prevail, if the clinical situation is consistent regardless of the MRI results. See p 671.
Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
Oxidative phosphorylation (OXPHOS) is the process that generates ATP, the primary carrier of energy in the cell. This process takes place in the mitochondrion and requires a number of different proteins, some encoded by mitochondrial DNA (mtDNA) and others encoded by autosomal (nuclear) genes. Anderson and colleagues sought to investigate whether variants within a larger set of OXPHOS genes encoded by both autosomal and mtDNA were associated with risk of ischemic stroke and intracerebral hemorrhage (ICH). After cumulative testing of all common genetic variation within OXPHOS loci by using a gene set enrichment analysis (GSEA) technique, they investigated whether the OXPHOS pathway was enriched for association with stroke risk. They then ascertained the role of these variants by calculating a genetic risk score from OXPHOS genes in the Massachusetts General Hospital (MGH) Ischemic Stroke GWAS (n=1843). The risk score association was replicated in a separate dataset (n=2632) comprised of individuals from the Ischemic Stroke Genetics Study (ISGS) and Siblings with Ischemic Stroke Study (SWISS). Finally, the same risk score was tested in ICH using individuals from the International Stroke Genetics Consortium ICH GWAS (ISGC ICH; n=1837). Blood samples from individuals of European ancestry were analyzed in the present study. Ninety-five genes in the autosomal genome and 13 genes in the mitochondrial genome encoding proteins directly involved in the OXPHOS respiratory chain were selected based on published criteria. Single-nucleotide polymorphisms (SNPs) falling within these genes (±100 kilobases) were extracted from the MGH and ISGS/SWISS datasets after imputation and included in the final analysis. Risk score quintiles were used as the independent variable in a logistic regression for the respective ischemic and ICH risk, whereas adjusting for age, sex, and other relevant clinical covariates. Among ischemic stroke subtypes, GSEA revealed significant associations between small vessel stroke and OXPHOS Complex I and IV. An association was found between deep ICH and Complex IV. In conjunction with prior investigations, these results highlight a genetic contribution to the risk for cerebral small-vessel disease and lacunar as well as deep hemorrhagic strokes. Such analyses further our understanding of the underlying etiopathology and may allow for future (individual) risk assessments if further refined. See p 612.
- © 2013 American Heart Association, Inc.