European Stroke Conference (ESC)May 6-9, 2014
May 8, 2014
There was a revolution in Transient Ischemic Attack (TIA) care in 2000 with the publication of the seminal report by SC Johnson and colleagues (JAMA 2000;284:29012906) of the high risks of stroke and vascular events following an index event. In the following years TIA risk scores such as the ABCD2 (Lancet 2007;369:283-292 ) were developed and promulgated throughout routine neurological care. At the European Stroke Conference in Nice Professor Pierre Amarenco presented the results of a modern TIA cohort collected through the use of the TIAregistry.org web-site, and the results were very interesting and likely to inform clinical practice.
The TIAregistry.org project evaluated short and long-term outcomes and refine risk assessment paradigms. Subjects had to be free of disability at baseline and have been evaluated for thei TIA in <7 days from onset, ideally <24 hours. A total of 4798 were recruited over 2.5 years: 4581 had complete data. The mean age was 66, 60% were men, 60% hypertensive and over half presented with a motor weakness syndrome. The ABCD2 scores were on the higher end with >70% scoring 4 or more. Imaging-demonstrated acute infarction was seen in 33% of cases, 16% had extracranial stenosis. Treatment was excellent with >90% on antithrombolic and >70% on antihypertensive and dyslipidemic agents. During follow-up <6% had a major vascular event, 4.7% had a stroke.
This study further validated the ABCD2 score in a real-world cohort obtained from a registry. Of note when the ABCD<4, 40% had a major finding (vessel stenosis, atrial fibrillation, infarct on imaging), when ABCD>=4, 75% had a major finding. Even in the low-risk group the hazard ratio for stroke was 3.5 when any major finding was revealed.
Although modern prevention therapy has cut the number or recurrent events by half, this important work demonstrates that TIA is a neurological emergency requiring immediate evaluation. The current paradigm is using the ABCD2 score to risk stratify, followed by screening of the brain with MRI, the cervical arteries, fasting lipids and heart rhythm monitoring. The timing and location of the evaluation may vary based on the risk score. TIAregistry.org has shown us that we have come a long way in preventing stroke after TIA, but it remains a dangerous and important disease process.
May 7, 2014
There were many interesting presentations at clinical trials session of the 23rd European Stroke Conference on May 6, 2014. One of the most interesting and important for clinical practice was the Efficacy of Nitric Oxide in Stroke (ENOS) study presented by Phillip Bath on behalf of the ENOS study group. This randomized study of over 4000 subjects had two main arms; the first was treatment with transdermal glyceryl trinitrate (GTN, nitroglycerine) vs. control and the second was continuation or discontinuation of home antihypertensive therapy in the acute stroke week. Each arm yielded findings relevant to clinical practice.
The GTN arm looked at the effect of BP lowering by transdermal nitroglycerine on death and dependency at three months and was neutral. GTN was safe and lowered BP by about 7mmHg systolic/4mmHg diastolic compared with control. The median time to enrolment was 26 hours. In subgroup analysis, the group treated <6 hours from onset seemed to show a benefit in outcome, whereas later time periods did not. This comes at the heels of the recently published The Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT, Stroke. 2013 (11) 3120-8) which demonstrated clinical benefits of BP lowering with transdermal GTN for stroke patients enrolled in the field in a time period < 4 hours. Does this mean that hyper-acute BP lowering is feasible and exciting to study in the future? Is there something about GTN which is particularly neuroprotective or beneficial in stroke? Does the combination of an early subgroup analysis of a large trial combined (ENOS) with an independent small pilot study (RIGHT) make the idea of acute BP lowering with GTN interesting for future study?
The second arm of premorbid antihypertensive stop or continue in acute stroke is very important question that we all deal with as clinicians. I tend to hold antihypertensive for a few days in the acute phase whereas my colleagues often continue the agents. In ENOS, the largest study to address this question, there was no difference in outcomes and the study was neutral for discontinuation vs. continuation. There were significant differences in BP in the two arms throughout the study, which indicates that the two groups were being treated differently. Of the adverse events, it appeared that those randomized to continuing antihypertensive pills in the presence of dysphasia had higher rates of pneumonia. This is probably the last study to answer this question and along with the earlier COSSACS indicate that continuing or stopping antihypertensive not affect outcome in acute stroke. Will this change your practice? I feel more confident in routinely withholding antihypertensive pills for a few days, but would never withhold statin. Stopping statin in the acute phase is bad, stopping antihypertensive pills, not so bad.
I would think that the role of nitric oxide in synaptic plasticity would be much more relevant to stroke survivors.
The role of nitric oxide in pre-synaptic plasticity and homeostasis.
Front. Cell. Neurosci., 31 October 2013 | doi: 10.3389/fncel.2013.00190
Based on that what are the ways to generate NO in order to help survivors? Does strong humming generate enough NO for those purposes? How long do you have to spend in sunlight to generate enough NO? Whom is going to create the stroke protocols for these items?