Capsular Warning Syndrome: Features, Risk Profile, and Prognosis in a Large Prospective TIA Cohort

Abstract

<b><i>Introduction:</i></b> Features and prognosis of capsular warning syndrome (CWS) have been poorly investigated prospectively. <b><i>Aims:</i></b> The study aimed to characterize CWS clinical features, risk profile, short- and long-term prognosis, among a large TIA cohort. <b><i>Methods:</i></b> Prospective cohort study of consecutive TIAs was conducted from August 1, 2010, to December 31, 2017. Demographic and clinical characteristics, risk profile, primary (stroke and composite outcome) and secondary (TIA recurrence, cerebral hemorrhage, new onset atrial fibrillation) outcomes were compared between CWS, lacunar (L), and nonlacunar (NL) TIAs. <b><i>Results:</i></b> 1,035 patients (33 CWS, 189 L-TIAs, 813 NL-TIAs) were enrolled. Newly diagnosed (ND) hypertension, hypercholesterolemia, cigarette smoking, and leukoaraiosis were independent risk factors of CWS (<i>p</i> < 0.05). CWS showed the highest stroke (30.3% vs. 0.5% and 1.5% for L-TIAs and NL-TIAs, respectively) and composite outcome risk at follow-up (<i>p</i> < 0.001), but better 3-month post-stroke prognosis (mRS 0–2 90.0% vs. 36.8%; <i>p</i> = 0.002). CWS-related stroke mostly occurred <48 h (80.0%) and had a small vessel occlusion etiology (100%), affecting more often the internal capsule (60.0%). Dual antiplatelet therapy (DAPT) versus single antiplatelet therapy was associated with lower 3-month cumulative stroke incidence (12.5% vs. 57.1%; <i>p</i> = 0.010). Intravenous thrombolysis (IVT) showed similar 3-month efficacy and safety in strokes after TIAs groups (median mRS 0, IQR 0–1; <i>p</i> = 0.323). <b><i>Conclusions:</i></b> CWS is associated with higher stroke risk and better functional prognosis than L- and NL-TIAs. CWS risk profile is consistent with severe small vessel disease, and ND hypertension could represent a major risk factor. DAPT and IVT seem effective and safe in preventing and treating stroke following CWS.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke

“…‘Progressive lacunar stroke’ is defined quite variably, including as an increase in NIHSS of ⩾2 points within 72 h 106,107 or ⩾3 points in total and ⩾2 points for limb paresis within 5 days, 108 or ⩾4 in total,109, 110 or ⩾2 by 48 h 111 or the seventh day after admission, 112 or ⩾1 within 5 days of onset, 113,114 or ⩾1 115,116 in the NIHSS, or ‘any persistent neurological worsening’. 117 Capsular warning syndrome (‘capsular’ or ‘stroke warning syndrome’) is variously defined as ‘⩾3 118–121 or ⩾2 122 stereotyped episodes of lacunar symptoms within 24, 48, or 72 h, with complete neurological resolution between episodes’. ‘Stuttering’ or ‘fluctuating’ lacunar syndrome’ is defined as ‘neurologic deficit’ with periods of improvement and worsening (with or without full resolution).…”

Treatment of progressive ischemic stroke with low‑dose eptifibatide: A retrospective case‑control study

“…MCA, middle cerebral artery; ACA, anterior cerebral artery; PCA, posterior cerebral artery; NIHSS, National Institutes of Health Stroke Scale; ∆NIHSS improvement, NIHSS at progression compared with 7 days after treatment; dual antiplatelet, aspirin 100 mg/day combined with clopidogrel hydrochloride 75 mg/day; monoclonal antiplatelet, aspirin 100 mg/day. capsular warning syndrome (CWS), since CWS is most often due to small penetrating vessel hemodynamic disorder (25,26).…”

“…SAO-associated stroke is known to be caused by small arterial hyalinosis, endothelial dysfunction and/or intracranial perforator atherosclerosis ( 23 , 24 ). SAO is a common cause of capsular warning syndrome (CWS), since CWS is most often due to small penetrating vessel hemodynamic disorder ( 25 , 26 ). A previous study on tirofiban showed that it could stop early symptomatic fluctuations and decrease the duration of functional impairments in patients with CWS compared with oral antiplatelet drugs ( 27 ).…”