Imprecise eponyms in stroke medicine – A growing need for uniform terminologies/definitions across the globe
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.258048
Source of Support: None, Conflict of Interest: None
Keywords: Cerebrovascular accidents, cerebrovascular attack, cerebrovascular disease, cerebrovascular events, cerebrovascular insult, stroke, transient ischemic attack
Stroke is the second leading cause of death worldwide in the low-middle and high-income countries, the leading cause of death in upper-middle-income countries, and also the leading cause of disability worldwide. Remarkable advancements in the understanding of etiological risk factors and the pathophysiology of cerebrovascular diseases have been observed in the last three decades but are deemed to be slow and inadequate compared with the progress in cardiovascular diseases. Increased and rapid refinement of guidelines and updates have been noted in cerebrovascular medicine during the last 15 years. Stroke being the second leading cause of death and the first leading cause of disability worldwide, the terminologies used in stroke medicine are still extremely variable and diverse, with many of them being extremely imprecise. Few of them are being extensively used, but are only defined according to the individual study requirements.
It would be difficult or impossible to estimate the exact usage of different terms in routine clinical practice across the world, especially due to the fact that the vast majority of stroke cases are being grossly underestimated and underdiagnosed in the developing countries. In this article, we describe the trends in literature, regarding the usage of different terminologies in stroke medicine in reference to the widely accepted classification of “cerebrovascular disease” and the recently updated definitions of “stroke” and “TIA.”
A systematic search was performed in Google Scholar for the words “stroke,” “TIA,” cerebrovascular accident,” “cerebrovascular insult,” “cerebrovascular event,” “cerebral ischemia,” and “cerebrovascular disease.” Each of words was searched year-wise from 1996 to 2015, and the exact number of articles using these words were noted. A line chart was obtained using the data, with the year designated on the y-axis, and the number of articles using the given word on the x-axis. Google Scholar was preferred as the search engine to include both indexed and nonindexed journals, whereas the search in Medline and Cochrane Library yielded only indexed articles, which were very few in number. For example, the search results for the word “cerebrovascular accident” in Medline yielded 2520 articles between 1995 and 2015, whereas the numbers were 54,700 articles in Google Scholar during the same period. Moreover, it was assumed that the search in Google Scholar would be nearer to global trends (as the search includes both low-mid income countries and high-income countries) than a search performed in Medline.
The collected and analyzed data showed a progressive increase in the number of articles published in stroke medicine. “Stroke” was the most common terminology used in literature, which showed a progressive increase in its usage until 2010, after which its use drastically reduced [Figure 1]. “Cerebrovascular events” and “cerebrovascular disease” were the second most commonly used terminologies; there was a steep increase in the use of these words until 2012, after which there was a sharp fall in the trend to use this word. The other words were less often used but showed a constant and a slow upward trend [Figure 2]. Many terms with no specific definitions like “cerebrovascular accident/cerebrovascular attack” are being used quite frequently.
The definitions of various terminologies in stroke are constantly evolving; however, assessing how these changing definitions are being understood and used by clinicians and researchers across the world from time to time is immensely challenging. Using uniformly defined definitions is essential for the overall quality of data in the literature; this, in turn, could pave a way for the development of guidelines and recommendations.
The analyzed data showed a clear increase in the number articles (indexed and nonindexed) in the field of stroke medicine, which implies a progressive increase in awareness and interest in stroke medicine among clinicians and researchers. However, it has been observed that the words 'cerebrovascular accident/cerebrovascular attack' lack a clear definition and continued to be used in literature, and possibly in clinical practice as well. On the other hand, a clearly defined word like 'cerebrovascular disease' is being misinterpreted and misused in the literature and continues to be accepted by the reputed international journals. The other group of words 'cerebrovascular events' and 'cerebrovascular insult' are the direct counterparts of cardiovascular medicine and defined according to the needs of the study in focus, without being uniformly defined. The word 'stroke' is the most used terminology, the usage of which increased progressively till 2012, beyond which there has been a sharp decrease in the usage of the word. The possible explanation for the decrease in its usage after 2012 is likely due the articles being more research focussed on specific subtypes of strokes, and hence, the usage of precise terminologies like “posterior circulation infarct,” silent infarcts, “aneurysmal SAH,” etc., started replacing the generalized term 'stroke'. TIA is now a well-recognized and defined entity; the increased usage of this term could also be possibly contributory to the reduced use of the term 'stroke'. The third possibility could be the frequent use of terms like 'cerebrovascular events/insult' in clinical trials in order to combine the two clinical events, stroke and TIA, into a single term.
Stroke as a distinct neurological entity was first described by Hippocrates (460–370 BC), the father medicine. The Greek word “apoplexy,” coined for this entity by Hippocrates, meaning “struck down with violence,” continued to be used for all episodes of strokes till the 1920s, when the word 'cerebrovascular accident (CVA)' was substituted for 'apoplexy'. Both of these words, 'CVA' and 'apoplexy' are imprecise and inappropriate. The word 'stroke' was introduced by Willian Cole as early as in 1689; its use became more widespread only in the late 20th century, the definitions of which continued to change/evolve till 2013. The early attempt to define 'stroke' in the 1970s was by World Health Organisation (WHO), which stated that stroke consists of “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting for more than 24 hours or leading to death, with no apparent cause other than that of vascular origin”. The American Heart Association/American Stroke Association (AHA/ASA) updated the definition of stroke in 2013, which stated that “the term 'stroke' should broadly be used to include all of the following: (i) Central nervous system (CNS) infarction, (ii) ischemic stroke, (iii) silent CNS infarction, (iv) intracerebral hemorrhage, (v) silent cerebral hemorrhage, (vi) subarachnoid hemorrhage, (vii) stroke caused by subarachnoid hemorrhage, (viii) stroke caused by cerebral venous thrombosis, and (ix) stroke, not otherwise specified.” Further, each of these components of stroke is defined and explained in detail. The European guidelines have not given a separate definition for stroke, and probably continue to use the WHO definition.
Transient ischemic attack
The term “transient ischemic attack” was accepted in 1965, at the Fourth Princeton Cerebrovascular Disease Conference, though the definition was published in 1975 by the Ad Hoc Committee on Cerebrovascular diseases. The accepted definition was that “transient ischemic attacks are episodes of temporary and focal dysfunction of vascular origin, which are variable in duration, commonly lasting from 2 to 15 minutes, but occasionally lasting for as long as a day (24 hours). They leave no persistent neurological deficit.” The definition of TIA was changed in 2002 to “transient ischemic attack (TIA): a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting for less than one hour, and without evidence of acute infarction,” by the Working Group. This definition was further refined by the AHA/ASA in 2009 to “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction”. Apart from these two definitions given by WHO and AHA/ASA, no other large scientific bodies have attempted to define the terms 'stroke/TIA'.
The aim of precisely articulating these definitions was to avoid confusion among clinicians regarding decisions pertaining to the performing of various diagnostic imaging and blood tests, to stratify the risk, and to assess prognosis. While all these definitions were evolving and being refined, the clinicians across the globe used an “easy” terminology to cover all aspects of the ischemia/infarct-related symptoms into one group, 'cerebrovascular accident'. Whether or not the term 'CVA' includes both 'stroke' and 'TIA', or only 'stroke', has not been not clearly defined anywhere. The word 'cerebrovascular accident' is being used synonymously with “clinical neurological disease due to any cerebrovascular disease” for several decades. When the meaning of each word in this term is analyzed separately, the definition of “accident” as described in Oxford dictionary is “an unfortunate incident that happens unexpectedly and unintentionally, typically resulting in damage or injury,” whereas the meaning of 'cerebrovascular' pertains to 'vessels related to the brain (both large and small vessels)'. However, when both the words are combined and their meaning is sought, the meaning of the phrase would be more defined as an “unexpected stroke” or a “stroke that happened unexpectedly”! After decades of advancements in medicine and the development of understanding about the pathophysiology of stroke, it is now well established that stroke is caused not by chance (accident), but by many of the risk factors. 80% of these factors can be treated, if detected early, to prevent the occurrence of stroke.
As the quote goes “If you repeat a lie often enough, it becomes the truth,” the word 'CVA' seems to be more accepted and is becoming a more popular word than the word 'stroke' and 'TIA' by both clinicians and researchers. Several other questions related to the word 'CVA' remain unanswered since decades: 1) What does a patient and common man think/understand about the word “accident” in 'CVA'? 2) Does it make the physician's job of educating the patients and the common man regarding 'stroke' more difficult?3) Does it make primary prevention (in asymptomatic individuals) of 'stroke' more difficult? The issues are of paramount importance in less-literate populations like those prevalent in the low and middle-income countries than in high-income countries. Of course, the word 'CVA' is deeply entrenched in the vocabulary of many countries, and hence, changing the trend and avoiding the use of these words is not easy; however, journals and conference meetings/continued medical educations programs are the best places to start implementing this change. There is an imminent need for the authors, editors, reviewers, and publishers to understand the different terminologies and promote the use of precise nomenclature in stroke medicine.
When literature search was carried out focused upon the corresponding equivalent word for 'coronary vascular disease' (e.g., cardiovascular accident), the latter word was not used in scientific literature, but was noted in nonscientific literature represented by the acronym 'CVA'. While searching for a corresponding word in peripheral vascular diseases (e.g., peripheral vascular accident) or mesenteric vascular disease (e.g., mesenteric vascular accident), it was discovered that no such phrases exist!. In fact, other than the phrase 'road traffic accidents', the word 'accident' is only used in literature when something happens unexpectedly, more often suddenly. In spite of few of the authors discouraging the use of the term 'cerebrovascular accident' for 'stroke',,,, the term continues to be used by physicians, neurologists, and other clinical practitioners worldwide. The term also continues to be used in renowned textbooks like Harrison's Principles of Internal Medicine. Thus, it has become deeply rooted in the minds of medical graduates right from the inception of their careers. Even the WHO continues to use the term 'stroke' and 'cerebrovascular accident' on their website under the “health topics.” However, the term 'cerebrovascular accident (CVA)' has not been used in the International Code of Diseases 9th and 10 Clinical Modification (ICD-9-CM, ICD-10CM), which was published by the WHO. Though the ASA/AHA did not promote the use of the word 'CVA', the association also did not condemn its usage by physicians and researchers, as evidenced by the continued acceptance of word 'CVA' in the articles submitted to the journal 'Stroke',,,, and 'Circulation,' the prominent cardiovascular journals., In total, 1,099 articles published in the journal “Circulation” used the term 'CVA'. The word 'CVA' also continued to be used in many other indexed and nonindexed journals as well. In fact, the usage of the word 'CVA' in journals has steadily increased over the last 20 years [Figure 2] and [Figure 3] (graph plotted from results searched on an yearly basis for the articles containing 'CVA' in Google Scholar). This trend shows the lack of implementation of the accepted terms among both clinicians and researchers, with the accentuated use of the traditional and inappropriate words still continuing.
Cerebrovascular insult and cerebrovascular events
Lately, many other terminologies are being increasingly used by physicians and researchers, namely, 'cerebrovascular insult' and 'cerebrovascular events', presumably to include both 'TIA' and 'stroke'. These two terminologies were probably a direct derivative of the vocabulary used by their cardiac counterparts, who often use the terms 'cardiovascular insult/events'. Even though these terminologies are not described in detail, they are widely accepted and used. A few questions remain unanswered. Do the terms 'cardiovascular insult/events' include silent strokes also or only clinically defined/identified events. These terminologies are the more preferred terminologies in clinical trials, and probably include only clinical events; the definitions, however, vary across trials. Further adding to the confusion, in certain articles of indexed journals, it is also observed that 'stroke' is considered as a cardiovascular event., There is no doubt that certain cardiac disease like atrial fibrillation can serve as an aetiology for stroke; however, it is not wise to include stroke as a cardiovascular event. Otherwise, statements like the insular stroke inducing cardiac arrhythmias, or an aneurysmal subarachnoid hemorrhage-induced myocarditis (Takotsubu myocarditis) may also need to be included as a 'cerebrovascular disease', which is definitely not the case in the clinical scenario.
Interestingly, some unscientific terminologies mimicking well-defined scientific terminologies are also being used, like 'cerebrovascular attack', probably a word denoting a similar meaning as the “brain attack.” The latter term has been used with an intent to explain the manifestations of stroke to common people in an easily understandable language. The word was used in approximately 68,100 articles in journals between the years 1995 and 2015. Though many of these are nonindexed journals, many indexed journals have also accepted this terminology.
The word 'cerebrovascular disease' comprises a heterogeneous group of diseases involving large, medium, and small cerebral vessels, that may be a manifestastion of an inflammatory, neoplastic or infectious etiology, of which stroke (ischemia/infarct/haemorrhage) is only a part-manifestation of the group. An elaborative classification of these etiologies was published in 1990 by the National Institute of Neurological Disorders and Stroke (NINDS). Interestingly, even this word, though seemingly straightforward (includes all diseases affecting the cerebral vasculature), has been misrepresented in multiple articles related to cerebral microvasculopathy, or stroke., It is also essential to make the journal reviewers and researchers understand that the term 'cerebrovascular disease' pertains to a group of diseases and does not necessarily only mean the presence of a 'microvascular disease/stroke'. Moreover, it is time to further revise the classification to include newer entities like cerebral amyloid angiopathy-related inflammation. Advancements during the last 25 years in the research in the field of dementia and Parkinson's disease have linked vascular causation factors to the development of these diseases, and therefore, these disease can also be added to the spectrum of cerebrovascular diseases.,,
Ischemic infarct and secondary haemorrhage
The other groups of definitions are related to the occurrence of haemorrhage within or outside of an acute infarct. Hemorrhagic conversion of acute infarct is seen in groups either receiving or not receiving tissue plaminogen activator (tPA), which may affect the prognosis depending upon the size and extent of haemorrhage. This phenomenon is described using the common terminology “hemorrhagic transformation”. A differentiation between 'asymptomatic' and 'symptomatic hemorrhagic transformation' was made based on the clinical deterioration attributable to the underlying hemorrhage in stroke patients in the NINDS trial and Multicenter Acute Stroke Trial of Italy and Europe. However, the European Cooperative Acute Stroke Study (ECASS) classified hemorrhagic transformation based on radiological and clinical criteria into hemorrhagic infarct (HI) 1 and 2, and parenchymal hematoma (PH) 1 and 2, for their study purpose. The third type of hemorrhage, remote parenchymal hematoma (PHr), was introduced by Trouillas and von Kummer in 2006. This modified classification involving three types of hemorrhages in acute stroke patients is widely accepted and used; however, there is need for a consensus statement that helps in standardizing these terminologies across the world for the uniform use of these terms in all future stroke trials.
The use of various terms and definitions across the world is responsible for the lack of production of uniform data in the stroke medicine. While many low and middle-income countries lack their own definitions and guidelines, they tend to follow the different terminologies and definitions set by the developed nations [Table 1]. There is a need, for international organisations like the WHO or the World Stroke Organisation (WSO), to derive useful data from different societies and give guidelines and terminologies that can be used by various nations all over the world. Now that the WHO has approved WSO as one of their non-governmental organizations (NGOs), and WSO is actively involved with WHO to revise ICD-10 to ICD-11 (http://www.world-stroke.org/about-wso/wso-at-the-un), it is only a matter of time before WSO resolves/eliminates multiple confusing/conflicting terminologies and derives uniform codifications and definitions in stroke medicine. Implementing the usage of translational medicine (bench-to-bedside medicine) is definitely challenging; however, more important is to implement uniform terms and definitions in the already well-understood part of the clinical stroke medicine.
There are diverse terminologies used in stroke medicine, particularly for research purposes which are imprecise and not defined properly anywhere in the literature, that are being continuously used by clinicians and researchers. The most imprecise term being used is 'cerebrovascular accident'. Even precisely defined entities like 'cerebrovascular diseases', which are a group of diseases classified in 1990, are being used inappropriately. It is essential to condemn the use of imprecise terminologies and promote the use of recently defined precise terms 'stroke' and 'TIA'. Unless the same terms with precise definitions are used in clinical practice or literature, the progress in stroke medicine will continue to be hampered.
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There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]