• Vol. 43 No. 1, 11–14
  • 15 January 2014

Wake-up Stroke and Onset-to-door Duration Delays: Potential Future Indications for Reperfusion Therapy


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Introduction: There is limited utilisation of acute stroke reperfusion treatments which have narrow therapeutic windows, with delayed hospital presentation being a major limiting factor in Singapore. Most patients who wake up with symptoms are ineligible for reperfusion treatments as duration from onset time is not known. We studied the profile of wake-up strokes, onset-to-door duration and their associated factors among ischaemic stroke patients in the context of potential new treatments.

Materials and Methods: This is an observational study of consecutive ischaemic stroke patients presenting within 2 weeks of symptom onset to the Singapore General Hospital in 2012.

Results: Of the 642 ischaemic stroke patients studied, 33% of the cases were wake-up strokes [median age 64 years, 88% <80 years; median NIHSS score 4, 98% <20]. The median onset-to-door duration was 14.3 hours (Interquartile range, 4.8 to 38.2 hours), 20% of them arrived <3.5 hours (considering eligibility for intravenous alteplase in the proven 4.5 hours window accounting for a one hour door-to-needle duration), 14%: ≥3.5 to <8 hours, 11%: ≥8 to <12 hours, and 56%: ≥12 hours. Most patients with known stroke risk factors including atrial fibrillation (66%), hypertension (78%) and prior stroke (81%) presented beyond 3.5 hours.

Conclusion: The one- third proportion of wake-up stroke in this cohort and low prevalence of relative contraindications suggest this is a promising group for emerging thrombolysis indications. With the majority of patients presenting after 8 hours, widening of the therapeutic window with new potential reperfusion treatments would not appreciably increase treatment utilisation. This study reaffirms the urgent need for public education to improve stroke awareness in Singapore.

In ischaemic stroke, acute reperfusion therapy aims to recanalise arterial obstruction leading to salvage of hypoperfused cerebral tissue with the goal of improving clinical outcomes. Reperfusion treatments include intravenous thrombolysis with alteplase which is licensed within the narrow therapeutic window of 4.5 hours, novel intravenous fibrinolytics which are under trial, and interventions such as intra-arterial thrombolysis and mechanical thrombectomy which are currently not licensed for acute stroke treatment. Worldwide, utilisation of reperfusion therapies is low, with only 2% to 4% of ischaemic stroke patients receiving intravenous thrombolysis. Similarly in Singapore, less than 5% of ischaemic stroke patients receive intravenous thrombolysis, with the main limitation being presentation beyond the therapeutic time window. In addition, stroke patients who wake up with neurological deficits (wake-up strokes) are a therapeutic dilemma. As their stroke onset time is unknown, they are often ineligible for intravenous thrombolysis and studies have reported lower recanalisation rates and worse functional outcomes.

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