The Consensus Statement includes two parts, the Consensus Statement itself, and the Recommendation to the European Stroke Organisation (ESO) on revision of ESO Guidelines. Please note that the final text of the Guidelines, is decided by ESO and that the recommendation in this document may not be the final guidelines version. As soon as the guidelines are confirmed, they will appear on this website as well as on the ESO website www.eso-stroke.org

A. Karolinska Stroke Update Consensus Statement

TIA – still a clinical definition?

The following Consensus Statement was adopted by the 7th Karolinska Stroke Update meeting on November 17, 2008.

The consensus statement was proposed by the chairman of the session, Dr Peter Ringleb, Heidelberg, the co-chair Professor Ljiljana Bumbasirevic, Belgrade, and the session secretary Dr Ruben Tamazyan, Paris, together with the speakers of the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.
The speakers in this session were Professor Bo Norrving, Lund, and Professor Peter Kelly, Dublin.

Controversy to discuss at the 2008 consensus session:

Should ’TIA’ be redefined or renamed?
How should a TIA be defined – clinically based or tissue based?

Background

The classic definition of transient ischemic attack (TIA) is a sudden, focal neurological deficit that lasts for less than 24 hours, is presumed to be of vascular origin, and is confined to an area of the brain or eye perfused by a specific artery. The 24 hour limit is also part of the WHO definition, which defined a stroke as “a focal neurological impairment of sudden onset, and lasting more than 24 hours (or leading to death), and of presumed vascular origin” and a transient ischemic attack with symptoms lasting less than 24 hours. During the last years several studies have demonstrated that TIA are medical emergencies because of a high risk of a recurrent stroke with permanent disability [2, 6]. However both health professionals and the public tend to consider TIAs benign, whereas they regard strokes as serious. A renaming of the term TIA and the use of terms like ‘ministrokes’, ‘warning stroke’, may underscore the need for urgent action when a patient has symptoms of acute brain ischemia [1]. Because TIA is a commonly used term we are concerned that introduction of a new term may cause some confusion thus we believe that the term requires redefinition rather than replacement.

Several studies have demonstrated that many patients with completely resolved clinical symptoms have lesions on CT or MRI, especially on diffusion weighted imaging (DWI). It also has been shown that the presence of those DWI-lesions correlates with several clinical features known to predict stroke risk after TIA [5]. However, there are only limited data, demonstrating an increased risk for stroke recurrence in DWI-positive patients as compared to patients with normal brain imaging [3, 4].

Discussion

Statement in favour of a clinically based TIA-definition:

For the patient it is the clinical symptoms that matter in the end. Demonstration of infarct may carry some extra prognostic information, but this is of little use in clinical practice and does not influence therapeutic decisions.

The term TIA is well embedded in clinical routine and also in large parts of the community. We can easily deal with the issue of transient symptoms due to limited tissue loss within the current framework of terms.

The idea to have a tissue based definition of TIA (or rather a tissue based definition of cerebral infarction: yes or no) is logically sound and appealing, and would be equivalent to the recent redefinition of myocardial infarction: infarction = documented tissue loss. However, the cardiologists have reliable and inexpensive, easy-to-use diagnostic tests available for this purpose (tissue loss: yes or no?) – at present this is not the case for the stroke field.

We know that CT scan is useless in the acute phase to identify permanent tissue loss. Even conventional MRI cannot resolve this issue in the acute phase. With time, the sensitivity of CT and conventional MRI to define cerebral infarction reaches similar magnitudes. However, far from all patients with chronic stroke with residual symptoms (logically due to tissue loss) have a documented tissue loss with these techniques.
In the individual case difficulties in separating new symptomatic infarcts from old silent ones are not uncommon.

Acute DW-MRI cannot be used for this diagnostic purpose: DW-MRI is highly sensitive in the acute phase to delineate ischemia, but ischemia does not equal infarction. We have no technique to reliably identify infarction in the acute phase; this requires use of follow-up imaging studies. About half of all TIAs have a DW-MRI abnormality but the sensitivity is likely dependent of field strength.  Follow-up studies of patients with TIA and DW-MRI ischemic abnormalities show that an infarct cannot be documented on late MRI examinations in about a quarter of all cases. At least 15 % of all strokes are DW-MRI negative; in 1 study 40 % of all lacunar infarcts were DW-MRI negative. There is currently no biomarker available to reliably identify tissue loss in the acute phase.
Adopting a stringent classification of cerebral infarction would require late, follow-up imaging. The demonstration of tissue loss is not reliable in the acute phase. The need to delay diagnosis setting to the post-acute phase is clinically very impractical.
If diagnostic criteria should be closely followed (and why shouldn’t they) adopting a change would incur use of acute DW-MRI and follow up MR (or CT) at a cost which cannot be prioritized. Today few patients with TIA and stroke are examined with all these techniques routinely. For Sweden implementation of extra imaging tests would cost 8000 pats x 1000 EURO = 8 million Euros for TIA alone, and even much more if extended to large proportions of those with residual symptoms. This amount is not justified from a practical point of view, money could be much better spent than on a theoretical issue of no therapeutic importance.

In summary,

• a tissue based definition of cerebral infarction is certainly logically appealing
• However, we don’t have reliable imaging or lab tests available at present for use in the acute phase. There are sensitivity/specificity problems both for patients with transient and permanent symptoms.
• Large scale implementation of extra diagnostic tests only for theoretical purposes would be very costly, of no use for management, and would receive a low priority.
• The cardiologists changed with the availability of adequate tests for routine use in acute phase – the stroke field is not there yet. The current terminology framework works fine meanwhile, no reason to rush, let’s wait. A new definition should not be introduced at a wrong time.

Statement in favour of a tissue-based TIA-definition:

Should TIA be re-defined or re-named?

For healthcare professionals, researchers, and insurance payers:  Keeping the term TIA is preferable to describe symptoms, presumed ischaemic, without other cause or objective evidence of permanent ischaemic injury (clinical signs perhaps unnoticed by the patient, positive DWI, or perhaps abnormal serum markers in the future).

For communication with the general public:  To emphasise the urgency of both stroke and TIA, and because it is often unclear initially that symptoms will resolve, the term 'Brain Attack' would be more suitable to cover all ischemic brain syndromes when we are communicating with the general public.

Limitations and strengths of the ‘traditional’ clinical definition:

Limitations:

1. Differences exist between different versions of the traditional definition, depending on the primary intended use (e.g. clinical practice or epidemiological research).
   For example, the 1975 NIH definition describes ‘episodes of temporary and focal cerebral dysfunction of vascular origin….of variable duration….commonly 2-15 minutes but occasionally as long as 24 hours. No residual neurological deficit’. No mention of ocular symptoms is made and the definition implies that all symptoms and signs have resolved. In contrast, the Oxfordshire Community Stroke Project definition includes disturbance of ocular function, but does not specify a requirement for resolution of clinical signs, suggesting that patients with persistent unnoticed signs (e.g. facial asymmetry) are classified as TIA and not stroke.

2. The current definition may contribute to a perception among non-specialist physicians and the public in some healthcare settings that TIA does not require urgent treatment.

3. Neuroimaging studies indicate that 30-60% of clinically-defined TIA have evidence of permanent ischaemic brain injury.

Strengths:

1. The traditional definition is clinically-based, equally suitable for use in healthcare settings with few and many neuroimaging resources.

2. It provides a useful common definition for clinical and epidemiological studies, allowing valid comparisons and providing clarity to promote development of policy and services.

Improving diagnostic precision in TIA:

Two problems exist with TIA diagnosis in clinical practice:

1. Distinguishing transient neurological symptoms related to ischemia from those due to non-ischemic causes.

2. Distinguishing transient ischemic symptoms with no evidence of permanent tissuedamage, from those with permanent tissue damage.

Improved precision may be of particular value to distinguish non-ischaemic from ischaemic transient symptoms, as prognosis, management strategies (and cost) may differ substantially. In this regard, it may be clinically useful and cost-effective to perform diagnostic testing such as MRI. However, further research is required to investigate whether MRI has additional benefit over clinical assessment alone to distinguish patients with transient ischaemic and non-ischaemic symptoms.

A 2nd issue arises when distinguishing transient symptoms with and without permanent identified ischemic injury. Current evidence supports similar strategies for secondary prevention in both categories. However some studies suggest that positive DWI in individuals with transient ischaemic symptoms may have a role in risk stratification of patients at high and low risk for early recurrent stroke. In the future, it is possible that a positive DWI scan in patients with transient ischaemic symptoms may influence clinical care decisions for individual patients – for example, the risk of early recurrent stroke in patients with positive DWI may be sufficiently high to warrant hospital admission for immediate treatment in the event of early recurrence. Further research is required in patients with transient ischaemic symptoms to investigate the role of positive DWI in influencing clinical decision-making.

Accuracy of 1.5T DWI in TIA:

Although DWI performed on 1.5T MRI is the most widely-available sensitive technique for detection of minor ischaemic injury in clinical practice, several limitations remain. False negative DWI may occur in true TIA and small stroke, or if the interval between symptom onset and DWI is too early or late (with possible resolution of DWI hyperintensity). False positive DWI may occur due to ‘shine-through’ of old lesions, or mimic conditions (e.g. focal seizures).
 
In the clinical setting of minor or more severe stroke, animal studies and one small study in humans suggest that DWI has high diagnostic accuracy, particularly high specificity, for detection of pathologically-verified infarction, including small infarcts. A few early studies have reported persistence of DWI hyperintensity on serial MRI, consistent with permanent ischaemic injury. Therefore, in patients fulfilling clinical criteria for TIA, DWI hyperintensity is likely to indicate infarction in most cases. Further research is needed to determine the diagnostic accuracy of 1.5T MRI in the clinical setting of TIA.

Proposal for a ‘tissue-based’ definition:

TIA is a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with symptoms typically* lasting <1 hr (*but not exclusively) and without evidence* (*clinical signs, imaging or other) of acute infarction’                      

Strengths and limitations of the proposed ‘tissue-based’ definition:

Strengths:

1. It gives the patient primacy over other users - Provides best diagnosis available for individual patients
2. It is closer to the true pathophysiology of TIA – ie. transient ischaemia, not minor ischaemic stroke
3. It provides flexibility for the time period – use of ‘typically’ rather than ‘always’ allows exceptions to the one-hour period
4. It provides flexibility for the requirement for neuroimaging – brain imaging is not mandatory. If no clinical signs and imaging not performed, then a suitable event is assigned as TIA
5. It may increase the urgency of TIA management - redefining TIA to emphasise exclusion of acute stroke is likely to communicate to non-specialist physicians that all ischemic syndromes should be considered a stroke until proven otherwise, possibly leading to increased urgency with referral and management of all minor stroke/TIA

Limitations:

1.  Variable TIA classification in clinical and epidemiological research is likely, depending on the extent of clinical and imaging evaluation. This will limit comparability of studies
2. Techniques for demonstration of infarction remain sub-optimal, so some patients with minor infarction may continue to be mis-classified as TIA

Conclusion

• Short lasting neurological or retinal symptoms presumable of vascular origin should still be named as transient ischemic attack (TIA); even this established term is not perfect. Typically – but not exclusively – the clinical symptoms last less than one hour.
• Because of lack of a ‘perfect’ biomarker for brain damage there is no possibility for an operational definition. For special situations like clinical trials more complex definitions might be helpful, e.g. using diffusion weighted imaging as a substitute of proven brain damage.
• All researchers should report the definition for transient symptoms used, maybe more complex definitions are useful for clinical trials.
• Every patient with a suggested TIA is an emergency. Public and professional education must be improved to increase the awareness of the emergency situation. F
• Further research should be performed to improve the diagnostic precision of techniques to detect minor cerebral infarction and investigate the effects of demonstrated infarction on risk stratification for early recurrent stroke after TIA.

 

References:

1. Albers GW, Caplan LR, Easton JD et al. (2002) Transient ischemic attack--proposal for a new definition. N Engl J Med 347:1713-6.
2. Giles MF, Rothwell PM (2007) Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol 6:1063-72
3. Prabhakaran S, Chong JY, Sacco RL (2007) Impact of abnormal diffusion-weighted imaging results on short-term outcome following transient ischemic attack. Arch Neurol 64:1105-9
4. Purroy F, Montaner J, Rovira A et al. (2004) Higher risk of further vascular events among transient ischemic attack patients with diffusion-weighted imaging acute ischemic lesions. Stroke 35:2313-9.
5. Redgrave JN, Coutts SB, Schulz UG et al. (2007) Systematic review of associations between the presence of acute ischemic lesions on diffusion-weighted imaging and clinical predictors of early stroke risk after transient ischemic attack. Stroke 38:1482-8
6. Rothwell PM, Coull AJ, Silver LE et al. (2005) Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 366:1773-83

 

 

B. Recommendation by Karolinska Stroke Update participants to ESO Guidelines Committee to revise ESO guidelines:

New text marked red


The 2008 ESO-Guideline does not contain a definition for the term TIA. We suggest a modification of the current guidelines by adding following statement.

 

Introduction


Stroke is one of the leading causes of morbidity and mortality worldwide [4]. Large differences in incidence, prevalence and mortality have been noted between Eastern and Western Europe. This has been attributed to differences in risk factors, with higher levels of hypertension and other risk factors resulting in more severe stroke in Eastern Europe [5]. Notable regional variations have also been found within Western Europe. Stroke is the most important cause of morbidity and long-term disability in Europe, and demographic changes will result in an increase in both incidence and prevalence. It is also the second most common cause of dementia, the most frequent cause of epilepsy in the elderly, and a frequent cause of depression [6, 7].


TIA is commonly defined as short lasting neurological or retinal symptoms presumable of vascular origin; although this long-used clinical definition is not perfect. A proportion of these patients may have an ischemic abnormality on acute diffusion-weighted magnetic resonance imaging (DWI-MRI) and a small infarct on late neuroimaging. Because of lack of a ‘perfect’ biomarker for brain damage in the acute phase a tissue-based definition of TIA is currently not practically feasible. For special situations, like clinical trials, more complex definitions might be helpful, e.g. using DWI-MRI as a marker of proven brain damage.


Many guidelines and recommendations for stroke management or specific aspects of stroke care have been published during the last decade [2,8,9,10,11,12,13,14,15,16,17,18]. Most recently, the updated Helsingborg Declaration focused on standards of stroke care and research needs in Europe [19]. In the future, the global harmonization of stroke guidelines will be the focus of the World Stroke Organisation, supported by the ESO and other national and regional stroke societies.

 


References:

2. The European Stroke Initiative Executive Committee and the EUSI Writing Committee: European Stroke Initiative Recommendations for Stroke Management - Update 2003. Cerebrovasc Dis 2003;16:311-337.
6. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, Redgrave JN, Bull LM, Welch SJ, Cuthbertson FC, Binney LE, Gutnikov SA, Anslow P, Banning AP, Mant D, Mehta Z: Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005;366:1773-1783.
7. O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST: Vascular cognitive impairment. Lancet Neurol 2003;2:89-98.
8. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF: Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655-1711.
9. Albers GW, Hart RG, Lutsep HL, Newell DW, Sacco RL: AHA Scientific Statement. Supplement to the guidelines for the management of transient ischemic attacks: A statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association. Stroke 1999;30:2502-2511.
10. Alberts MJ, Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg MR, Starke RD, Todd HW, Viste KM, Girgus M, Shephard T, Emr M, Shwayder P, Walker MD: Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA 2000;283:3102-3109.
11. Alberts MJ, Latchaw RE, Selman WR, Shephard T, Hadley MN, Brass LM, Koroshetz W, Marler JR, Booss J, Zorowitz RD, Croft JB, Magnis E, Mulligan D, Jagoda A, O'Connor R, Cawley CM, Connors JJ, Rose-DeRenzy JA, Emr M, Warren M, Walker MD: Recommendations for comprehensive stroke centers: a consensus statement from the Brain Attack Coalition. Stroke 2005;36:1597-1616.
12. Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole J, Easton JD, Adams HP Jr, Brass LM, Hobson RW 2nd, Brott TG, Sternau L: Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1998;29:554-562.
13. Diener HC, Allenberg JR, Bode C, Busse O, Forsting F, Grau AJ, Haberl RL, Hacke W, Hamann GF, Hennerici M, Grond K, Ringelstein B, Ringleb PA: Primär- und Sekundärprävention der zerebralen Ischämie; in Diener HC (ed): Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart, Thieme, 2005.
14. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC Jr, Alonso-Garcia A, Blomstrom-Lundqvist C, de Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A: ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration with the North American Society of Pacing and Electrophysiology. Circulation 2001;104:2118-2150.
15. Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, Culebras A, Degraba TJ, Gorelick PB, Guyton JR, Hart RG, Howard G, Kelly-Hayes M, Nixon JV, Sacco RL: Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:1583-1633.
16. Hacke W, Kaste M, Skyhoj Olsen T, Orgogozo JM, Bogousslavsky J: European Stroke Initiative (EUSI) recommendations for stroke management. The European Stroke Initiative Writing Committee. Eur J Neurol 2000;7:607-623.
17. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T: Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577-617.
18. The National Board of Health and Welfare: Swedish National Guidelines for the Management of Stroke, Version for Health and Medical Personnel 2000; article number 2002-2102-2001.

 


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