The Advances in Stroke section that has appeared yearly since 2003 has proven to be both popular and useful to the readership, providing concise reviews of important, novel information across a wide gamut of cerebrovascular topics. For 2006 the section editors of Stroke were asked to overview their areas of expertise. Additionally, the fifth Stroke Therapy Academic Industry Roundtable (STAIR) meeting took place early in 2006 and the main topics of discussion are summarized.
Information about genetic contributions to the development of a variety of cerebrovascular disorders continues to emerge. Collagen gene mutations that predispose to the development of hemorrhages in mice were identified. In humans, several genetic abnormalities related to the development of intracranial aneurysms emerged. Previous studies suggesting a highly significant relationship of phosphodiesterase 4D and ischemic stroke appear to have been blunted by studies that appeared in 2006 not supporting this relationship.
Therapeutics for cerebrovascular disorders experienced important advances and also bitter disappointments in 2006. The major advances were in the realm of secondary prevention where the ESPRIT trial confirmed prior evidence that aspirin and extended-release dipyridamole confers additional benefit regarding secondary stroke prevention in comparison to aspirin monotherapy. The SPARCL trial of atorvastatin demonstrated that 80 mgs daily of this HMG-CoA reductase inhibitor significantly reduced the risk of recurrent stroke and also coronary ischemia in stroke patients. The major disappointment in the therapeutic realm was the failure of the second large clinical trial of the free-radical spin-trap drug, NXY-059, to replicate the positive results seen in the first phase III trial reported earlier in 2006. The SAINT trials were well designed and performed and the negative results of SAINT-II will need to be carefully analyzed so that clues as to how to better perform future neuroprotection trials can be discerned, if possible.
Stroke prevention remains an area where substantial progress continues to be made. The relationship of elevated homocysteine and atherosclerotic disorders including ischemic stroke is firmly established. For both primary and secondary stroke prevention, recent trials have not demonstrated that interventions with B-vitamins and/or folic acid appear to reduce risk. In prior studies, patent foramen ovale (PFO) was demonstrated to be related to cryptogenic stroke, especially in younger patients. However, recently this potential relationship has been questioned. The optimal approach for the treatment of PFO patients to reduce secondary stroke risk remains uncertain and the results of ongoing trials comparing device closure and antithrombotic therapy are much anticipated. The provision of health services to maximize stroke risk reduction in transient ischemic attack (TIA) patients remains a concern, especially in the United Kingdom, based on information provided by recent publications. Public awareness about TIA symptoms also remains lacking and educational efforts need to be enhanced.
Critical care of patients with cerebrovascular disorders is a rapidly emerging discipline with far reaching implications. More rapid clinical and imaging evaluation in the emergency department provides the opportunity to potentially treat more stroke patients acutely. For large middle cerebral artery strokes with mass effect, evidence continues to emerge that decompressive hemicraniectomy reduces mortality and may also be associated with improved clinical outcome in survivors. Elevated blood glucose levels are associated with a worse outcome after stroke. Lowering of elevated blood glucose levels is beneficial for critically ill patients and studies in cerebrovascular disease patients are underway. In global cerebral ischemia after cardiac arrest, the benefits of hypothermia have been known for several years. However, the routine use of hypothermia for the treatment of this disorder has not been widely implemented, and this experience mirrors in some respects the slow adoption of intravenous tissue plasminogen activator (t-PA) for the treatment of ischemic stroke patients.
Health policy and outcome issues are becoming increasingly important to the cerebrovascular field. It is apparent that stroke care and patient outcomes are improved by the more widespread use of stroke care units, the greater use of intravenous t-PA and comprehensive secondary prevention strategies that encompass antithrombotic medications, tight blood pressure control, statin use and smoking cessation. A second Helsingborg declaration was crafted in 2006 that will emphasize these points. The lack of stroke trained and dedicated physicians and allied healthcare professionals remains problematic. For the physician component of the problem, additional and expanded training is clearly needed, and the use of advanced communication systems as exemplified by telemedicine should help to leverage the availability of scarce resources.
The use of interventional procedures for the treatment of cerebrovascular disorders is increasing rapidly. Additional information concerning the safety and reperfusion utility of the MERCI device appeared in 2006, along with preliminary information about an intravascular ultrasound device and its effect on recanalization. The risk/benefit ratio of carotid angioplasty/stenting may not be as favorable as previously suggested based on reported French study. The use of endovascular techniques for the treatment of intracranial aneurysm and arteriovenous malformations continue to evolve.
The role of neuroimaging continues to expand rapidly for guiding the evaluation and treatment of acute stroke patients. Identifying and quantifying the ischemic penumbra with MRI, CT and positron emission tomography (PET) is a fast developing area with broad implications for the future of acute stroke care, because there is widespread agreement that this potentially salvageable ischemic tissue is the target of acute stroke therapies. PET and diffusion/perfusion MRI (DWI, PWI) were correlated to determine the accuracy of the DWI/PWI mismatch for identifying the penumbra. Not surprisingly, it was observed that the mismatch over-estimated the extent of penumbral tissue, and it should be acknowledged that the DWI/PWI mismatch represents only an approximation of the ischemic penumbra. Several PET ligands can be used to identify the preserved neurons and penumbral tissue, but unfortunately these techniques will likely remain research tools. Advanced imaging techniques are also being applied to investigate brain recovery and the tracking of injected stem cells.
The field of stroke recovery and rehabilitation provided interesting insights recently. Studies, particularly with functional MRI, continue to demonstrate that functional reorganization reproducibly occurs after ischemic stroke. Functional integrity of the corticospinal tracts is particularly relevant for motor recovery. Learning and practice also contribute to motor recovery. The use of repetitive transcranial magnetic stimulation to facilitate poststroke recovery is an exciting new approach that will need to be validated in much larger clinical trials but appears to be a promising novel treatment strategy. The value of early mobilization to improve recovery remains questionable based on currently available data.
Vascular cognitive impairment (VCI) is assuming an increasing importance as exemplified by the recent harmonization conference that presented standards for the definition and study of this disorder. It remains unclear what the impact of blood pressure control is on the development of VCI. The extent of leukoaraiosis appears to be related to impairment of several domains of cognitive function, and the progression of leukoaraiosis is highly correlated with cognitive decline. A reasonable future approach to treatment trials of VCI to impede progression would therefore be to identify patients with progressing leukoaraiosis and more severe cognitive decline as the target population. Such secondary prevention trials are likely to require less follow-up time than studies that enroll less severely impaired VCI patients.
The pace of advances in the stroke field continues to accelerate, and we can anticipate yearly updates in Stroke for many years to come.
- Accepted December 11, 2006.