Syncope : an integrative physiological approach
Thijs, R.D.
Citation
Thijs, R. D. (2008, September 24). Syncope : an integrative physiological approach.
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27
Terminology and Classification
Unconscious Confusion.
A literature search for definitions of syncope and related disorders
Roland D Thijs,1 David G Benditt,2 Christopher J Mathias,3 Ronald Schondorf, 4 Richard Sutton,5 Wouter Wieling,6 J Gert van Dijk1
Clinical Autonomic Research (2005) 15: 35–39
[1] Department of Neurology and Clinical Neurophysiology, Leiden University Medical Centre, Leiden, The Netherlands
[2] Department of Cardiology, Cardiovascular Unit, University of Minnesota, Minneapolis, USA
[3] Autonomic Unit, University Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery, Queen Square and Institute of Neurology, University College London, UK
[4] Autonomic Reflex Laboratory, Department of Neurology, McGill University, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada
[5] Department of Cardiology, Royal Bromptom Hospital, London, UK [6] Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands
Chapter 1
30 Abstract
Background: Imprecise definitions of syncope and related conditions appear common in the medical literature. To investigate the scope of the problem we systematically searched for definitions in high-ranking medical journals.
Methods: Literature review of articles on ‘syncope’, ‘neurocardiogenic syncope’, ‘neurally mediated syncope’, ‘orthostatic intolerance’, and ‘orthostatic hypotension' with these key- words in the title, mainly published in the 10 journals with the highest impact in the fields of cardiology, internal medicine, and neurology.
Results: Syncope, neurocardiogenic syncope, neurally mediated syncope, orthostatic intolerance, and orthostatic hypotension were defined in only 41%, 34%, 26%, 38%, and 48%
of papers respectively. Definitions, when given, differed considerably among papers.
Orthostatic hypotension was most frequently defined, with an increase in number and consistency of definitions after publication of a consensus in 1996.
Conclusions: Syncope and related conditions proved to be infrequently and inconsistently defined in current medical literature. The lack of consistent terminology is likely to harm medical education, research, and patient care. There is a strong need for a systematic termino- logy for syncope and related conditions.
Chapter 1
Unconscious confusion
31 Introduction
For most medical practitioners, the term ‘syncope’ connotes a clinical picture which is intuit- tively readily grasped, but which is at the same time poorly understood. Recently, syncope was defined by consensus among specialists from various disciplines as a transient, brief, self- limited loss of consciousness due to a transient global cerebral hypoperfusion and usually leading to falling.28 The specific pathophysiology sets this definition apart from many other, less specific, definitions that remain in common usage.2,15,22,38 With imprecise definitions,
‘syncope’ may erroneously include various forms of epilepsy, concussion, hypoglycaemic attacks, or subarachnoid haemorrhage. Even feigned unconsciousness has been included within this excessively broad concept of syncope, resulting in misnomers such as ‘psycho- genic’ or ‘psychiatric syncope’.
The problem of terminology is not restricted to the definition of ‘syncope’ alone. The introduction of certain neologisms such as ‘neurally mediated syncope' and 'neurocardiogenic syncope' to compete with older terms such as vasovagal or reflex syncope, has created a plethora of terms that are commonly used interchangeably but were not so intended initially.
The inevitable risk is imprecise understanding of not only the pathophysiologic basis of syncope and related conditions but also their epidemiology and appropriate diagnostic evaluation. To investigate the scale of the problem, we undertook a systematic review of recent medical literature to determine whether the terms syncope, neurocardiogenic syncope, neurally mediated syncope, orthostatic intolerance, and orthostatic hypotension were defined, and, if so, how. Orthostatic hypotension was included to evaluate the influence of a published definition of relatively long standing on the consistency of use in medical literature.242
Methods
We used the PUBMED database to identify articles with one of the following keywords as a title word: ‘syncope’, ‘neurocardiogenic’, ‘neurally mediated’, ‘orthostatic intolerance’, and
‘orthostatic hypotension’. 'MESH headings' were not used, as these may link terms in unfore- seen ways (for instance, 'drop attacks' are interpreted as 'syncope'). The literature search included 100 recent papers with the keyword as a title word published in the 10 journals with the highest impact in the fields of cardiology, internal medicine, and neurology, according to the Journal of Citation Reports 2000 (Table 1). If fewer than 100 articles were obtained, an additional search was performed for the most recent articles with the keyword in the title in all
32
Table 1 The 10 selected journals with highest impact according to the Journal of Citation Reports 2000 in the field of internal medicine, cardiology and neurology
medical journals. Articles had to be in English and had to consider research on humans.
Editorials, brief communications and case reports were excluded. With regard to the keywords ‘neurocardiogenic’ and ‘neurally mediated’ the article had to be related to syncope, i.e., articles related to neurally mediated/ neurocardiogenic hypotension or other subjects were excluded. If syncope was defined but 'neurocardiogenic' or 'neurally mediated' was not, this definition was not included as a definition of a neurally mediated / neurocardiogenic syncope.
With regard to orthostatic hypotension the consistency of the provided defintion with the Consensus Statement was examined.242
The introduction and methods sections of the subject papers were reviewed for an explanation of the keyword in the form of a definition, a reference to a definition, or a synonym. Syno- nyms were noted if terms were used interchangeably. The papers were reviewed by one au- thor (RDT) and again by another (JGvD) when doubts arose.
Results
We identified 100 articles with ‘syncope’ (all in the top 10 journals), ‘orthostatic intolerance’
(12 in top 10), and ‘orthostatic hypotension’ (75 in top 10) as a title word. There were 77 articles with ‘neurocardiogenic’ (18 in top 10) and 70 articles with ‘neurally mediated’ (17 in top 10) as a title word. Eight out of 447 articles could not be found in Dutch scientific li-
Internal medicine Cardiology Neurology
Brit Med J Circulation Ann Neurol
New Engl J Med Circ Res Brain
JAMA J Am Coll Cardiol Brain Pathol
Annu Rev Med Eur Heart J Schizophrenia Bull
Ann Intern Med Cardiovasc Res Stroke
Arch Intern Med J Mol Cell Cardiol J Neuropathol Exp Neur
Am J Med Am J Physiol-Heart C J Clin Psychopharm
Lancet J Thorac Cardiov Sur Neurology
Medicine Trends Cardiovasc Med Arch Neurol
Amyloid J Cardiovasc Electrophysiol Pain Forum Chapter 1
Unconscious confusion
33 Table 2 List of synonyms
braries. Figure 1 displays the frequency of definition for each keyword and synonyms are listed in Table 2.
Syncope
Of all 100 articles, 41 (41%) gave a definition, 2(2%) provided a reference and 57 (57%) did not state a definition. If syncope was defined the following elements were mentioned:
unconsciousness (n=41, 100%), transient (n=39, 95%), self-limited (n=19, 46%), cerebral hypoperfusion (n=7, 17%), and short-lived (n=4, 10%).
Neurocardiogenic Syncope
Of all 77 articles, 26 articles (34%) gave a definition, 6 (8%) a reference, and 45 (58%) did not provide a definition. Definitions contained the following elements, in order of frequency:
hypotension (69%), bradycardia (59%), positive head-up tilt test (38%), inappropriate autonomic response (24%), prodromal symptoms (17%), and precipitating factors (3%). Three types of definition were recognised: ‘transient bradycardia and hypotension’ (n=14, 54%),
‘unexplained syncope with positive head-up tilt test' (n=10, 38%), and ‘syncope with typical prodromal symptoms’ (n=2, 8%).
neurocardiogenic syncope
vasovagal (syncope) (n=25), neurally mediated (syncope) (n=12), vasodepressor (syncope) (n=9), neurally mediated syncopal syndrome (n=1), carotis sinus syndrome (n=1), neurally mediated vasodepressor syncope (n=1), malignant vasovagal syndrome (n=1)
neurally mediated syncope
vasovagal (syncope) (n=16), neurocardiogenic (syncope) (n=13), vasodepressor (syncope) (n=5), cardioneurogenic (n=3), neurally mediated hypotension, reflex syncope (n=2), neurally mediated cardiac syncope (n=1), emotional fainting (n=1), pallid breath holding spells (n=1), white breath holding spells (n=1), pallid infantile syncope (n=1), vagal attack (n=1), reflex anoxic seizures (n=1), cardiovascular neurogenic (n=1), idiopathic syncope (n=1), neuroregulatory (n=1), malignant vasovagal syndrome (n=1).
orthostatic intolerance orthostatic hypotension (n=2)
34
Figure 1 The percentage of papers providing a definition (black), a reference (grey) and no definition of the keyword (white). S = syncope, NCS = neurocardiogenic syncope, NMS = neurally mediated syncope, OI = orthostatic intolerance, OH<1996 = orthostatic hypotension restricted to papers published before the Consensus Statement of 1996, OH>1996 = orthostatic hypotension restricted to papers published after the Consensus Statement of 1996.242
0 20 40 60 80 100
S NCS NMS OI OH<1996 OH>1996
%
Neurally Mediated Syncope
Of all 70 articles, 17 (24%) gave a definition, 52 (74%) no definition and 1 (1%) a reference.
If defined, the definition contained the following elements (in order of frequency): hypo- tension (58%), bradycardia (47%), abnormal autonomic regulation (35%), positive head-up tilt test (29%), prodromal symptoms (18%), precipitating factors (12%), positive response to carotid sinus massage (12%), or eyeball compression (6%). Two types of definition were recognised: ‘syncope due to transient bradycardia and hypotension’ (n=12, 71%) and
‘unexplained syncope with a positive head-up tilt test’ (n=5, 29%).
Orthostatic Intolerance
Of the 100 papers, 38 (38%) provided a definition and 62 (62%) did not. Table 3 summarises the various elements of these definitions.
Chapter 1
Unconscious confusion
35 Figure 2 Percentage of agreement of the definition of orthostatic hypotension with the Consensus Statement of 1996 divided for papers published before (white) and after (grey) the Consensus Statement .242
0 20 40 60 80 100
fall in SBP fall in DBP duration of standing
% agreement with consensus statement
Orthostatic Hypotension
Of all 100 articles, 48 (48%) defined orthostatic hypotension, 3 (3%) provided a reference, and 49 (49%) did not state any definition. Articles published before the Consensus Statement of 1996 defined orthostatic hypotension less frequently (33%) than articles published afterwards (67%). Figure 2 shows to what extent papers published before and after 1996 agreed with the Consensus Statement.
Table 3 The definition of orthostatic intolerance in 38 articles
Symptoms Heart Rate Blood Pressure Standing Noradrenaline
84% mentioned 63% tachycardia 34% no significant changes 84% mentioned 92% not mentioned 16% not mentioned 31% not mentioned 34% not mentioned 16% no remark 5% elevated
3% bradycardia 32% hypotension 3% normal/elevated 3% brady/tachycardia
36
Discussion
Syncope and its related conditions proved to be infrequently and inconsistently defined in current medical literature. The restriction of our literature search to title words assured that the term concerned a major subject of the article. The paucity of definitions is particularly remarkable in view of the fact that the search primarily encompassed the 10 journals with highest impact in the fields of cardiology, internal medicine, and neurology. The frequency with which orthostatic hypotension was defined was higher than for the other terms and the definitions used were more consistent than was true of other terms. We believe that this is mainly due to the Consensus Statement of 1996, as the definition rate improved after 1996.242
The problem
Definitions need obviously not to be given if a condition is so well known that confusion is unlikely. For instance, ‘myocardial infarction' will usually not require a definition. In our view this certainly does not hold for syncope and the associated concepts incorporated in this report, as we found a considerable lack of consistency among authors who did provide a definition. For example, salient features of the definition of syncope (its brief duration, its self-limiting character, and its causative mechanism) were frequently omitted. In fact, definitions often treated syncope as synonymous with 'transient loss of consciousness' (TLOC). The latter term may be more accurately used as a descriptive term for a common cli- nical presentation including, among others, syncope, some forms of epilepsy, and even conditions such as concussion resulting from head trauma.
We did not study whether or not authors actually used their definitions strictly. For instance, although a 'wide' definition (syncope defined as TLOC) might cause disorders such as con- cussion and epilepsy to fall under the 'syncope' heading, it was nevertheless evident that on many occasions where such a broad definition was provided a more restrictive definition seems to have been used. For example, the reported incidence of 'syncope' (defined widely) due to head trauma in the Framingham Heart Study concerned only 47 cases during 133,164 person-years.233 This low number suggests that not all cases of concussion were included, and implies that 'syncope' was sometimes interpreted in a wide and sometimes in a narrow sense.
The inclusion of some, but not all TLOC patients means that the resulting set of patients reflects neither the broad category of TLOC, nor syncope in the narrow sense.
Chapter 1
Unconscious confusion
37 With regard to orthostatic intolerance, there was little apparent agreement with regard to whether or not it was considered to be associated with hypotension. In fact, 'orthostatic intolerance' was used to describe three different concepts. The first was simply the occurrence of symptoms during standing, the second was the postural orthostatic tachycardia syndrome (POTS), and the third was orthostatic hypotension. It seems reasonable to take this term literally and therefore to restrict its use to symptoms during standing.28
A large number of terms including 'vasovagal syncope', 'vasodepressor syncope' ‘neurocardio- genic syncope’, and ‘neurally mediated syncope’ were frequently used as synonyms. The frequent usage (often incorrectly) of synonyms may obscure the clinical problem. By way of example, both neurocardiogenic and neurally mediated syncope frequently appeared to be used to describe a subtype of reflex syncope, namely patients with a clinically unexplained syncope and a positive tilt table test. Originally, these terms evolved in the cardiological literature to encompass all forms of ‘reflex’ syncope, of which conditions such as the vaso- vagal faint, carotid sinus syndrome, micturition syncope, etc., are subsets.
The lack of consistent terminology is likely to harm medical education, patient care, as well as research. Education suffers if the terms used to identify various causes of transient loss of unconsciousness are ambiguous and commonly misused. In patient care, this lack of precision may lead to a wasteful 'shotgun' approach, aimed at investigating all disorders that may cause syncope and even some that do not.39 Even more importantly, it undermines the acquisition of a stronger understanding of the nature of syncope. This causes confusion in distinguishing between syncope and epilepsy. For example, the diagnosis syncope could not be confirmed in 278 out of 641 patients referred for syncope to a tertiary care centre.169 Another example concerns syncope being mistaken for epilepsy: in the Holton inquiry, the General Medical Council reported a high rate of misdiagnosis of childhood epilepsy.267 Independent reviewing of all charts led to the conclusion that 32% of the patients of the consultant paediatrician were mistakenly given a diagnosis of epilepsy, leading to needless prescription of anticonvul- sants.268 Remarkably, this high rate of misdiagnosis rate was not thought to be unusual.43,268
Possible solutions
It is impossible to identify correctly the cause of every attack of transient loss of conscious- ness after the fact; it may even be impossible to establish that loss of consciousness actually
38
occurred with certainty.132 We feel that it is not prudent to use terms with specific patho- physiological connotations when faced with uncertainty. For such cases, we would prefer to use the phrase TLOC if unconsciousness has been clearly established. However, if not even that is certain we should not even use TLOC. The term syncope should be reserved for TLOC cases in which the specific probable cause, i.e., cerebral hypoperfusion, is at least likely.
Conclusion
There is a clear need for the development and widespread application of a systematic set of definitions not only for syncope itself but also its various associated conditions. Useful precedents are the classification systems of epilepsy or headache, reached by consensus.72,105 The example of 'orthostatic hypotension' illustrates the gain in consistency that can be obtained through a consensus statement.242
Since syncope can be caused by large array of disorders and diseases, it is essential that various medical specialities should take part in the definition process, including at the very least cardiologists, neurologists, and internists and probably also geriatricians, emergency physicians, general practitioners, and paediatricians. While none of the definitions of syncope and its associated conditions that we have encountered in the literature are necessarily inherently incorrect, the set of definitions reached by the European Society of Cardiology provides a basis that can be used until a wider consensus is reached.28
Chapter 1
