A Glimpse of Canaan, 40 Years On

Abstract

During the last few decades an explosion in definitions has occurred covering brief to permanent focal syndromes, diagnostic categories for stroke and subtypes, scoring systems characterizing clinical syndromes as well as imaging, and fostered the ascendancy of biostatistics and meta-analyses. These advances have led to the clinical trials which have changed the management, hyperacute therapy and prevention of recurrent stroke. Stroke trial design is now so well codified that its form is expected by the funding agencies, especially companies supporting trials. Despite criticism, transient ischemic attacks remain >24 h, uncommon diagnoses now fit into ‘stroke of other determined mechanism’, hyperacute treatment within 3, maybe 6 h is standard, as are outcomes at 30 days and 3 months. Unsettling to some, the randomized clinical trial may have reached a plateau in development. Clinical trials have also passed the point where outcomes can be measured in easily described events. The current problems find their focus in smaller cohorts, requiring multicenter efforts, nowadays spanning continents. They have also crossed into areas formerly considered the exclusive purview of sibling specialties, some members not predictably as concerned with the same research questions. Threats to the randomized clinical trial are also emerging in outcomes research. This approach is popular with agencies hoping to apply the widely accepted definitions to readily available clinical databases and will see only more use in times of limited budgets. One effect has been the unintentional restriction into the algorithms of new subtypes of ischemic and hemorrhagic stroke. Similarly, there has been insufficient focus on the effect of functional reorganization on poststroke clinical changes. It was long neglected when the clinical effects of lesions were inferred more or less permanent and explained as inferred ambidexterity, reversible tissue deactivation from edema and diaschisis. It was even explained that embolism was a transient process, leaving little brain injury in its wake. Long awaited, modern technologies are at last providing a means to study functional reorganization and compensatory mechanisms. Current results predict a radical change in our understanding of the course of syndromes from focal lesions, hopefully opening a new era for clinical neurology, maybe even a resurrection of semiology. Studies can be pursued in advance of lesions, during the poststroke course of living patients and for those planned for brain interventions, which could perturbate pretreatment functions and pathways. Those long dead would have envied us our current opportunity. Uncertain to be among those who reap the eventual harvest, this author is grateful for a glimpse of Canaan.

From C. Miller Fisher to MRI

“…1 During the following years, the Harvard Cooperative Stroke Registry standardized Miller Fisher's approach to evaluation of stroke patients using the then-new CT technology. 2 Mohr and Caplan, together with other stroke neurologists, started the new era of clarification of stroke mechanisms and classification of stroke syndromes and subtypes. 2 However, it soon became clear that many ischemic stroke patients remained whose strokes occurred without a clear mechanism, despite the use of best diagnostic tools at that time.…”

“…2 Mohr and Caplan, together with other stroke neurologists, started the new era of clarification of stroke mechanisms and classification of stroke syndromes and subtypes. 2 However, it soon became clear that many ischemic stroke patients remained whose strokes occurred without a clear mechanism, despite the use of best diagnostic tools at that time. A category of ischemic stroke of undetermined cause or cryptogenic stroke was created.…”

“…A category of ischemic stroke of undetermined cause or cryptogenic stroke was created. 2 Using the data from the National Institute of Neurological and Communicative Disorders and Stroke/Stroke Data Bank, Sacco et al 3 demonstrated that a great proportion of those patients with stroke of undetermined cause shared clinical and radiologic characteristics with those having infarct due to embolism.…”