Stroke Acute Management and Recovery

Over the last several decades the management of cerebrovascular disease has changed dramatically. Great advances in our understanding of the natural history, risk factor conditions, and pathophysiology have led to improved prevention, treatment, and intervention therapies. These changes have been both incremental and dramatic. Nonetheless, we still have much to learn about stroke and related conditions. In preparing these volumes, I challenged the authors in this issue of Seminars in Neurology and its companion issue (to be published in early 2006) to provide an update on various topics focusing on the translation of basic science, epidemiology, health services, and clinical research into clinical practice. Rather than recapitulate the current state of our knowledge found in typical reviews of the management of cerebrovascular disease, I wanted the authors to provide a glimpse of the near future. The current issue focuses primarily on cerebrovascular diseases and their consequences. The next issue will focus more on risk factor conditions, vascular biology, and genetics. I intentionally chose authors who are active participants in this research. Some are established leaders in their field and others are new researchers striving to answer important questions about stroke. Although not a complete list, the Table of Contents includes many of the rising stars who will continue to contribute to cerebrovascular neurology for decades.

This issue opens with three articles focused on acute care. Andrew Russman's and Irene Katzan's article reviews acute stroke treatment in the community setting. The approval of intravenous (IV) tissue plasminogen activator (t-PA) for use as acute treatment for ischemic stroke was one of the most significant paradigm shifts in the care of stroke patients.[1] However, some critics raised concern about translating the clinical trial protocol to effective clinical care. Dr. Katzan's work analyzing the use of IV t-PA at community hospitals in the Cleveland metropolitan area both gave some credence to those concerns[2] and proved that educational interventions are effective in improving the delivery of evidence-based acute stroke care in a community setting.[3] Furthermore, recent data suggest that the public health impact of IV thrombolysis is limited both in the academic[4] and in the community[5] setting. Drs. Russman and Katzan provide an analysis of the options for improving the effectiveness of acute stroke care in the community setting through community awareness, establishment of local acute stroke treatment protocols, academic-community partnerships, and telemedicine.

Doojin Kim and David Liebeskind review recent advances in neuroimaging and how these new technologies are transforming acute stroke care. Acute radiological evaluation of stroke is much more than noncontrast head computed tomography. Drs. Kim and Liebeskind provide excellent examples of how imaging can rapidly and accurately demonstrate the type and extent of cerebrovascular injury to guide therapy. They provide an excellent balance of discussing the state-of-the-art and emerging technologies.

In 2000, Clay Johnston was lead author on a very important paper that demonstrated that transient ischemic attack (TIA) carried significant and imminent risk, warranting prompt evaluation and treatment.[6] Subsequent and parallel studies confirmed this finding in numerous settings.[7] [8] [9] In this issue, Dr. Johnston reviews the current management of TIA and some of the proposed mechanisms for the extreme vulnerability of patients with transient neurological symptoms.

The next two articles focus on optimal management of patients with patent foramen ovale (PFO) or atherosclerotic carotid disease. There is little data to guide recommendations for patients with cryptogenic stroke and a PFO. In contrast, there are extensive data on management of carotid disease. However, in both cases controversies abound and consensus is rare. Carole Thomas, an active participant in efforts to address these gaps in our knowledge, reviews the current state of knowledge on PFO. She highlights the need for rigorous data to guide management of the frequently young patients with PFO and stroke. Kumar Rajamani and Seemant Chaturvedi examine the results of completed and ongoing clinical trials on carotid atherosclerosis through the lens of recent advances in medical management. Dr. Chaturvedi has previously advocated for a reexamination of the management of carotid disease now that medical management is far more comprehensive and multidimensional.[10] Both of these articles highlight the challenges practicing neurologists face when selecting treatment strategies for these patients.

The next two chapters focus on complications of cerebrovascular disease that are commonly left to nonneurologists. John Krakauer provides an important discussion of the neurobiology of recovery after stroke and its relationship to motor learning. He rightfully calls on neurologists to reclaim poststroke care and promote a more scientific and patient-specific approach to rehabilitation. He challenges many of the tenets of poststroke disability and encourages empirical testing of rehabilitation strategies. Linda Williams addresses the challenge of poststroke depression, including difficulties in establishing the diagnosis and assessing the effectiveness of treatment on stroke outcomes, both areas where she has made significant contributions.[11] [12]

The next two articles confront an area that is all too often ignored in discussions of cerebrovascular disease: perinatal and pediatric stroke. John Lynch, Christina Han, Yvonne Wu, and Karin Nelson outline the current understanding of the epidemiology of stroke in these age groups based largely on work from their respective groups. They underscore the fundamental absence of data in many areas and frequent misperceptions, especially with regard to treatment and outcome. At the International Stroke Conference in San Diego in February 2004, several of these individuals participated in a symposium on these topics, calling for a systematic and comprehensive approach to this poorly researched area. They have made important contributions that serve as the foundation of their articles.[13] [14] [15] [16] [17]

This issue closes with two articles focusing on hemorrhagic stroke. An entire separate issue could be devoted to hemorrhage. Javier Provencio and Nirav Vora examine some of the clinical implications of bench research in the role of inflammation and subarachnoid hemorrhage. The role of inflammation has been widely accepted in ischemic stroke and atherosclerosis. Drs. Provencio and Vora provide compelling arguments that imbalances in the inflammatory pathway play a role in all aspects of aneurysmal subarachnoid hemorrhage. Amytis Towfighi, Steven Greenberg, and Jonathan Rosand discuss evaluation and promising treatments of intracerebral hemorrhage (ICH), which is the second most common type of stroke and the one with the fewest treatment options. These authors have focused their research on spontaneous and warfarin-related ICH. [18] [19] [20] The recently reported phase II trial of recombinant factor VIIa for acute ICH offers hope for specific therapy for ICH that will potentially alter the course of this often devastating type of stroke.[21] The authors explore pathophysiology and susceptibility with an eye toward potential prevention and treatment interventions.

In conclusion, this year marks the inauguration of the newly recognized subspecialty of vascular neurology by the American Board of Psychiatry and Neurology. I hope that this and the companion issue generate enthusiasm among the young readers for the exciting and broad field of cerebrovascular disease neurology. For those practicing neurologists and other practitioners taking care of stroke patients, I expect that these articles will provide a sense of excitement and optimism for the future of cerebrovascular medicine.

REFERENCES

• 1 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke.  N Engl J Med. 1995;  333 1581-1587
• 2 Katzan I L, Furlan A J, Lloyd L E et al.. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience.  JAMA. 2000;  283 1151-1158
• 3 Katzan I L, Hammer M D, Furlan A J, Hixson E D, Nadzam D M. Quality improvement and tissue-type plasminogen activator for acute ischemic stroke: a Cleveland update.  Stroke. 2003;  34 799-800
• 4 Johnston S C, Fung L H, Gillum L A et al.. Utilization of intravenous tissue-type plasminogen activator for ischemic stroke at academic medical centers: the influence of ethnicity.  Stroke. 2001;  32 1061-1068
• 5 Katzan I L, Hammer M D, Hixson E D, Furlan A J, Abou-Chebl A, Nadzam D M. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke.  Arch Neurol. 2004;  61 346-350
• 6 Johnston S C, Gress D R, Browner W S, Sidney S. Short-term prognosis after emergency department diagnosis of TIA.  JAMA. 2000;  284 2901-2906
• 7 Kleindorfer D, Panagos P, Pancioli A et al.. Incidence and short-term prognosis of transient ischemic attack in a population-based study.  Stroke. 2005;  36 720-723
• 8 Rothwell P M, Warlow C P. Timing of TIAs preceding stroke: time window for prevention is very short.  Neurology. 2005;  64 817-820
• 9 van Wijk I, Kappelle L J, van Gijn J et al.. Long-term survival and vascular event risk after transient ischaemic attack or minor ischaemic stroke: a cohort study.  Lancet. 2005;  365 2098-2104
• 10 Chaturvedi S. Should the multicenter carotid endarterectomy trials be repeated?.  Arch Neurol. 2003;  60 774-775
• 11 Williams L S, Brizendine E J, Plue L et al.. Performance of the PHQ-9 as a screening tool for depression after stroke.  Stroke. 2005;  36 635-638
• 12 Williams L S, Ghose S S, Swindle R W. Depression and other mental health diagnoses increase mortality risk after ischemic stroke.  Am J Psychiatry. 2004;  161 1090-1095
• 13 Fullerton H J, Wu Y W, Zhao S, Johnston S C. Risk of stroke in children: ethnic and gender disparities.  Neurology. 2003;  61 189-194
• 14 Lee J, Croen L A, Backstrand K H et al.. Maternal and infant characteristics associated with perinatal arterial stroke in the infant.  JAMA. 2005;  293 723-729
• 15 Wu Y W, March W M, Croen L A, Grether J K, Escobar G J, Newman T B. Perinatal stroke in children with motor impairment: a population-based study.  Pediatrics. 2004;  114 612-619
• 16 Lynch J K, Hirtz D G, DeVeber G, Nelson K B. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke.  Pediatrics. 2002;  109 116-123
• 17 Nelson K B, Lynch J K. Stroke in newborn infants.  Lancet Neurol. 2004;  3 150-158
• 18 Flibotte J J, Hagan N, O'Donnell J, Greenberg S M, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage.  Neurology. 2004;  63 1059-1064
• 19 Greenberg S M, Eng J A, Ning M, Smith E E, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage.  Stroke. 2004;  35 1415-1420
• 20 Rosand J, Greenberg S M. Beyond hypertension: unraveling the causes of intracerebral hemorrhage.  Stroke. 2002;  33 1195-1196
• 21 Mayer S A, Brun N C, Begtrup K et al.. Recombinant activated factor VII for acute intracerebral hemorrhage.  N Engl J Med. 2005;  352 777-785