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Show NEURO- OPHTHALMOLOGY AT LARGE The 2006 International Stroke Conference Orlando, Florida February 15- 18, 2006 The 2006 International Stroke Conference was held in Orlando, Florida on February 15- 18, 2006. Researchers from across the world gathered to discuss more than 500 abstracts presented as posters or platform presentations. Abstracts are published in Stroke 2006; 37: 620- 750. The presentations of special interest are summarized here. ACUTE ISCHEMIC STROKE Neuroprotective agents shown to be effective in animal models of acute stroke have been found to be ineffective in human clinical trials. Thus, the recently published Stroke- Acute Ischemic NXY Treatment ( SAINT I) trial ( N Engl J Med 2006; 354: 588- 600) is a welcome change because it provides the first evidence of clinical efficacy of a neuroprotective agent in humans. Trial results were discussed in detail by Kennedy R. Lees, MD, Glasgow University, with additional commentary and discussion provided by other experts in the field. In the trial, 1,722 patients with acute ischemic stoke presenting within 6 hours of symptom onset were randomly assigned to a placebo or a 72- hour infusion of NXY- 059, a free radical-trapping agent with proven efficacy in improving infarct size and outcome in animal models of stroke. Those presenting within 3 hours could also be treated with intravenous t- PA if they met thrombolytic eligibility criteria. The primary outcome measure was the modified Rankin Scale at 90 days. Patients receiving NXY- 059 showed an odds ratio for improvement of 1.20 ( 95% confidence interval [ CI]: 1.01- 1.42). Statistical significance for the secondary end points of the Barthel Index and NIH Stroke Scale was not reached, although there was a trend favoring active treatment in all outcome measures. An intriguing aspect of the trial was that patients treated with NXY- 059 and intravenous t- PA had a significantly lower rate of symptomatic intracerebral hemorrhage than patients treated with intravenous t- PA alone ( 2.5% versus 6.4%, P = 0.036). Although the clinical effect of NXY- 059 was modest, cautious optimism is warranted because of the favorable safety profile and the expanded time window for treatment. An additional trial of NXY- 059 in acute ischemic stroke ( SAINT- II) is currently ongoing in a larger population, including centers in North America. Patients with mild stroke symptoms are often excluded from treatment with intravenous t- PA with the assumption that they will have an excellent outcome without additional treatment. Nicole Gonzales, MD, University of Texas at Houston, presented results of that center's experience of patients excluded from thrombolytic treatment because of an NIH Stroke Scale score of ^ 7. Among 238 patients, 41 ( 17%) received intravenous t- PA. Patients who received t- PA were more likely to have an excellent outcome defined as no significant disability at discharge ( odds ratio: 2.47, 95% CI: 2.0- 5.1). Of patients given t- PA, 59% had an excellent outcome compared with 44% of those who were untreated. There were no symptomatic intracerebral hemorrhages or deaths in the treated group. The study is limited because it is a single-center, retrospective, non- randomized analysis and did not control for disabling symptoms such as isolated aphasia that may have influenced treatment decisions. However, these results, together with similar findings in other studies, suggest that physicians may wish to reconsider withholding t- PA treatment on the basis of mild symptoms. STATINS AND STROKE HMG CoA reductase inhibitors (" statins") are widely used for the treatment of hyperlipidemia and prevention of vascular events. There is an emerging body of evidence suggesting that their anti- inflammatory and vasodilatory properties may be beneficial in stroke prevention independent of their effects on low- density lipoprotein cholesterol. Several abstracts discussed possible benefits of statins in the acute phase of ischemic stroke. Atsushi Shiraishi, Tokyo Medical and Dental University, presented a non- randomized trial of consecutive Japanese patients admitted for stroke or transient ischemic attack in which outcomes were assessed related to statin use. In that trial, 5.2% of the 38 patients treated with statins before admission experienced worsening of neurologic status during hospitalization ( defined as s2 points worsening on the NIH Stroke Scale in 48 hours) compared 156 J Neuro- Ophthalmol, Vol. 26, No. 2, 2006 Neuro- Ophthalmology at Large J Neuro- Ophthalmol, Vol. 26, No. 2, 2006 with 21.5% of the 350 patients not pre- treated with statins ( P < 0.01). This study did not comment on how many patients continued or underwent withdrawal of statin therapy at the time of admission to the hospital. Florentino Nombela, Hospital Universitario de La Princesa, Madrid, presented results from a randomized, open- label study of statin withdrawal during hospitalization for acute ischemic stroke. During the first 3 days of hospitalization for new stroke, 89 patients were randomized to statin withdrawal ( group A) or to continued current statin treatment ( group B); 126 patients were not taking statins on admission ( group C). After 3 days, all patients began 20 mg atorvastatin daily. The three groups were well matched, except that non- statin users at admission more frequently had a cardioembolic source of their stroke, whereas statin users more commonly had a stroke as a result of large-artery atherosclerosis. The patients in the group randomized to acute statin withdrawal had a higher frequency of early neurologic deterioration, defined as > 4- point worsening of their NIH Stroke Scale score within 48 hours ( group A: 65.2%; group B: 20.9%; group C: 27.8%; P < 0.0001). In addition, they experienced a worse functional outcome, defined as moderate disability ( modified Rankin score > 2) at 3 months ( group A: 58.7%; group B: 37.2%; group C: 42.1%, P = 0.001) as well as larger infarct volume on head CT ( P < 0.0001). This study showed that patients randomized to statin withdrawal fared worst on all three outcome measures. However, patients who had never received a statin fared worse than those in whom statin therapy was continued. The same stroke researchers presented separate data that showed that the inflammatory response is increased during acute statin therapy withdrawal as measured by increased levels of IL- 6 and VCAM- 1 and decreased levels of 15d- PGD2. Thus, inflammatory rebound could be a mechanism contributing to deterioration after abrupt statin withdrawal. These two studies suggest that stroke outcomes may be modified by pre- treatment with a statin and by continuation of pre- existing statin therapy during acute hospitalization for ischemic stroke. They do not address whether patients experiencing acute stroke who are not pre- treated with a statin benefit from immediate initiation of statin therapy. Further study of larger populations is required before a widespread change in practice is warranted. STROKE REHABILITATION Stroke is the leading cause of long- term adult disability in the United States, and effective methods of rehabilitation for stroke survivors are sorely needed. Constraint therapy, which involves constraining the non-impaired arm and subsequent " forced use" of the impaired arm, has been shown to improve function in the chronic (> 1 year) phase of stroke rehabilitation but has not been evaluated in the subacute phase of stroke. Steven Wolf, PhD, Emory University, presented results of the multi-center Extremity Constraint Induced Therapy Evaluation ( EXCITE) trial. Stroke survivors with limb weakness 3 to 9 months after stroke were randomized to immediate or delayed constraint therapy in a single- blind crossover design. Patients randomized to the delayed intervention received the same therapy 1 year after randomization. The study intervention consisted of 2 weeks of constraint of the non- impaired arm during waking hours and 6 hours of training of the weaker arm on weekdays. Patients were assessed at baseline and every 4 months thereafter with rigorous training of study personnel to ensure consistent application of the functional assessment measures. Patients randomized to constraint therapy showed a sustained benefit at follow- up on standardized laboratory measures of extremity function as well as on measures of real- world functional use of the extremity. This therapy has the potential to help many stroke survivors improve their functional status with little or no risk of adverse effects. Darin B. Zahuranec, MD Jennifer J. Majersik, MD Department of Neurology University of Michigan Health System Ann Arbor, Michigan 157 |
