Giuseppe Reale, MD1,2; Marco Moci, MD2.
1Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Neuroriabilitazione ad Alta Intensità
2Università Cattolica del Sacro Cuore – Roma, Dipartimento di Neuroscienze
Transient Ischemic Attack (TIA) is usually characterized by transient focal neurological signs such as speech disturbances, hemiparesis or partial visual loss, without any neuroimaging evidence of cerebral ischemia1,2. Short-term risk of stroke after TIA is high: according to the most used score for assessing such risk, ABCD2 score, the risk of stroke within the first 48 hours ranges from 1% to 8.1%, depending on symptoms, their duration, patients’ age, hypertension and diabetes3. However, not all focal neurological signs are the same. This is the case of Capsular Warning Syndrome (CWS) that constitutes a subgroup of all TIAs. First described by Donnan et al in 1993, CWS consists of acute, transient, stereotypical sensory and/or motor symptoms affecting the face, arm and/or leg. There has to be an absence of cortical signs and it has to occur within a seven-day period after an index TIA4–6.
The most comomn manifestation of CWS is with a pure hemiparesis, the number of episodes mostly ranging between 3 to 10 (even in a single day), their mean duration being about 6 minutes, and appearing in “clusters”4–6. Although CWS is only responsible of 1.5-4.5% of all TIAs, the risk of ischemic stroke is likely high, with an incidence ranging between 17% and 70%. A recent review even showed that 74% of these patients had infarction on neuroimaging, which is far above the 8% risk detectable with ABCD2 score4–6. The ABCD3-I score proposed in 2010 added occurrence of at least two TIAs – a so called ‘dual TIA’ – to the stroke risk score7–9 and this was later validated in a Chinese population. However, when the recurrences of symptoms in a patients with a CWS is regarded as a ‘dual TIAs’, the risk of subsequent stroke is likely underestimated10. Pathophysiological mechanisms that might explain such increased risk of ischemic stroke are still unclear. Several mechanisms might contribute to the ischemic damage, including penetrating small vessel disease, hemodynamic impairment, branch-artery disease, artery-to-artery embolism and peri-infarct depolarization6.
Regarding treatment, dual antiplatelet therapy is the mainstay for all TIAs, CWS included6,11,12. Other potential therapies are matter of investigation, such as intravenous tirofiban (overlap loading Clopidogrel 300 mg and Aspirin 100 mg), which has been suggested as a potential intervention toreduce fluctuations in CWS patients13. When a DWI-FLAIR mismatch on MRI in the acute symptomatic phase is present, choosing thrombolytic therapy is reasonable.
In conclusion, CWS represent a non-neglectable sub-group of TIAs, it is characterized by several episodes of transient subcortical neurological symptoms and has a high risk of stroke progression. Therefore, when evaluating a TIA, suspecting CWS could have a significant impact on patients’ management strategies, especially in terms of monitoring during the early stage.
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- Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, Sidney S. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369:283–292.
- Paul NLM, Simoni M, Chandratheva A, Rothwell PM. Population-based study of capsular warning syndrome and prognosis after early recurrent TIA. Neurology. 2012;79:1356–1362.
- Donnan GA, O’Malley HM, Quang L, Hurley S, Bladin PF. The capsular warning syndrome: pathogenesis and clinical features. Neurology. 1993;43:957–962.
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- Song B, Fang H, Zhao L, Gao Y, Tan S, Lu J, Sun S, Chandra A, Wang R, Xu Y. Validation of the ABCD3-I Score to Predict Stroke Risk After Transient Ischemic Attack. Stroke. 2013;44:1244–1248.
- Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY, Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N. Engl. J. Med. 2018;379:215–225.
- Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, et al. Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack. N Engl J Med. 2013;369:11–19.
- Li W, Wu Y, Li X-S, Liu C-C, Huang S-H, Liang C-R, Wang H, Zhang L-L, Xu Z-Q, Wang Y-J, et al. Intravenous tirofiban therapy for patients with capsular warning syndrome. Stroke Vasc Neurol. 2019;4:22–27.