Commentaries
of patients are attended out of the range of the 3h window for intravenous thrombolytic therapy and out of the first 6h recommended for the use of intra-arterial thrombolysis. [5] Despite the high benefits of t-PA administration, arterial re-vascularization is not achieved in 30-40% of patients and potentially life-threatening hemorrhagic complications occur in 5-10% of patients.[3] The SIST-MOST study is an observational pharmacosurveillance study carried out in different countries of the European Union, the objective of which is to assess the results of thrombolytic treatment with tPA within the first 3h after stroke onset in patients with well-defined inclusion criteria and attended in qualified centers, although without previous experience in the use of this treatment modality, with an expected follow-up of three years. This study will answer whether satisfactory results obtained in clinical trials are reproducible to clinical conditions of daily practice in medical centers without experience in the use of thrombolytic therapy.[6] Future challenges of thrombolytic therapy include a significant increase in the frequency of administration and use of this therapy, to increase arterial re-vascularization rates, to decrease the occurrence of post-treatment bleeding and to extend the therapeutic window for the inclusion of candidates to this treatment modality. In this respect, healthcare education continues to be an essential step to achieve the first goal. The administration of t-PA together with the use of ultrasound (known as sonothrombolysis) has shown to increase the frequency of arterial repermeabilization in preliminary studies. In addition, the therapeutic usefulness of third-generation thrombolytic drugs (tenecteplase, reteplase, lanoteplase, pamiteplase and staphylokinase) is potentially greater because of a higher resistance than t-PA to neutralization by t-PA endogenous inhibitors or a longer mean half life. Another therapeutic approach would be the concomitant use of conventional thrombolytic therapy and neuroprotector drugs with the aim of maximal preservation of the ischemic shadow territory limiting the extension of the cerebral infarcted area. The use of diffusion-perfusion MRI is a
further potential alternative, which may allow the administration of thrombolysis treatment independently of the temporal window in cases in which potentially recoverable cerebral tissue could be demonstrated. This would occur when cerebral ischemia in perfusion sequences is significantly greater than cerebral infarction visualized in the diffusion sequences (the so-called “mismatch” phenomenon). Mechanical disruption of thrombi by embolectomy is another potentially interesting possibility in non-responders to intravenous or intraarterial t-PA administration. Finally, the usefulness of plasma biomarkers related to the efficacy and safety of thrombolytic treatment and that would alert to the risk of hemorrhagic transformation[4,1] will be another future
challenge that will allow optimization and individualization of thrombolytic therapy in the patient suffering from an acute cerebral infarction.
m o fr d ns a lo tio n w lica o d ub e rf e w P m). r References fo kno .co le ed ow b la M dkn i a by e v a si ted w.m F os w D P te h (w is si h T a
Adrià Arboix
Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Viladomat 288, E-08029 Barcelona, Spain. E-mail:
[email protected]
1.
2.
3. 4.
5. 6.
Padma MV, Singh MB, Bhatia R, Srivastava A, Tripathi M, Shukla G, et al. Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: Efficacy and safety profile of 54 patients at a tertiary referral center in a developing country. Neurol India 2007;55:46-9. Wardlaw JM, Zoppo G, Yamaguchi T, Berge E. Thrombolisis for acute ischaemic stroke. Cochrane Database Syst Rev 2003;3:CD000213. Davalos A. Thrombolisis in acute ischemic stroke: Successes, failures and new hopesw. Cerebrovasc Dis 2005;20:135-9. Arboix A. Importance of the first 6 hours in acute cerebral ischemia. Conclusions. Present and Future (article in Spanish). Neurol Supl 2005;1:80-2. SIST-MOST. Available from: http://acutestroke.org/. Rubiera M, Ribo M, Delgado-Mederos R, Santamarina E, Delgado P, Montaner J, et al. Tandem internal carotid artery/middle cerebral artery occlusion. An independent predictor of poor outcome alter systemic trombolysis. Stroke 2006;37:2301-5.
Thrombolysis for acute ischemic stroke in India: Overcoming the challenges Good stroke care programs and making thrombolysis accessible and attainable for patients is of critical importance, particularly in the Indian subcontinent where stroke rates are amongst the highest in the world. Acute stroke care has improved greatly in the last decade, particularly after the National Institute of Neurological Disorders and Stroke (NINDS) study group showed that recombinant tissue plasminogen activator (rtPA) Neurology India | January-March 2007 | Vol 55 | Issue 1
administered within three hours after the onset of ischemic stroke symptoms improved patient outcomes.[1] However, delivery of this hyperacute therapy can be quite difficult, especially in developing nations where issues of stroke infrastructure and costs may obstruct efforts to set up efficient stroke care programs. In this issue of Neurology India, Padma et al[2] report their experience of 54 patients treated with rtPA over a four-year period in a 9 CMYK9
Commentaries
tertiary care hospital in India. Their experience mirrors the experience of many centers in North America, but also highlights some of the unique challenges to establishing acute stroke care in developing nations. Although rtPA is the established and approved treatment for acute stroke within three hours of symptom onset, many centers in North America have low rates of thrombolysis. Overall in the United States, it has been estimated that only 2-3% of stroke patients receive this therapy,[3] particularly due to patients being out of the limited therapeutic window.[4] However, it has also been shown that with dedicated stroke programs and stroke teams, the rate of thrombolysis can be increased, with some centers, including our own, reporting rates as high as 20%.[5] In order to establish stroke programs and achieve good rates of thrombolysis, neurologists must advocate for this therapy and work hard with local officials, radiology departments, and emergency room physicians and personnel to make this service available. In many ways, the challenges faced to establish stroke care are more difficult in India. For example, as noted by the authors, the lack of rapid processing for bloodwork would make most patients ineligible for treatment, as the results would not be available within the three-hour window. By carefully selecting their patients, they were able to administer rtPA with impressive door-to-needle times and had no reported symptomatic intracerebral hemorrhage, despite giving therapy without coagulation profiles or platelet counts. One should be cautious, as it should be noted that the most feared complication of thrombolytic therapy, symptomatic intracerebral hemorrhage, is higher when deviations for the NINDS tPA protocol occur.[6] However, due to the different circumstances faced by the treating physicians in India, such innovative approaches may be necessary and, as long as the safety of such approaches can be established,
they should be encouraged. In addition, continued campaigns to increase public awareness of stroke, improving the emergency medical systems to allow patients to arrive in time for therapy and producing cheaper, generic alternatives to commercially available rtPA are crucial to improve patients’ outcomes in the Indian subcontinent. We applaud the efforts of the authors and we are optimistic that with continued efforts such as this, India can be a leader in the practical application of acute stroke care in the developing world.
m o fr d References s a n lo tio n a w c i do ubl e P ). e fr w m r fo kno .co le ed ow b la M dkn i a by e v a is ted w.m F os w D P te h (w is si h T a
10 10 CMYK
Muhammad S. Hussain, Ashfaq Shuaib
Division of Neurology, Department of Medicine, University of Alberta, Canada. E-mail:
[email protected]
1.
2.
3.
4.
5.
6.
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581-7. Padma MV, Singh MB, Bhatia R, Srivastava A, Tripathi M, Shukla G, et al. Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: Efficacy and safety profile of 54 patients at a tertiary referral center in a developing country. Neurol India 2007;55:46-9. Alberts MJ, Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg MR, et al. Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA 2000;283:3102-9. Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, et al. Use of tissue-type plasminogen activator for acute ischemic stroke: The Cleveland area experience. JAMA 2000;283:1151-8. Katzan IL, Hammer MD, Furlan AJ, Hixson ED, Nadzam DM; Cleveland Clinic Health System Stroke Quality Improvement Team. Quality improvement and tissue-type plasminogen activator for acute ischemic stroke: A Cleveland update. Stroke 2003;34:799-800. Hill MD, Buchan AM; Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis for acute ischemic stroke: Results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005;172:1307-12.
Neurology India | January-March 2007 | Vol 55 | Issue 1
