Ischemic stroke with unknown onset of symptoms: current scenario and perspectives for the future

Abstract

Background Stroke is a major cause of disability worldwide and a neurological emergency. Intravenous thrombolysis and mechanical thrombectomy are effective in the reperfusion of the parenchyma in distress, but the impossibility to determine the exact time of onset was an important cause of exclusion from treatment until a few years ago.

Objectives To review the clinical and radiological profile of patients with unknown-onset stroke, the imaging methods to guide the reperfusion treatment, and suggest a protocol for the therapeutic approach.

Methods The different imaging methods were grouped according to current evidence-based treatments.

Results Most studies found no difference between the clinical and imaging characteristics of patients with wake-up stroke and known-onset stroke, suggesting that the ictus, in the first group, occurs just prior to awakening. Regarding the treatment of patients with unknown-onset stroke, four main phase-three trials stand out: WAKE-UP and EXTEND for intravenous thrombolysis, and DAWN and DEFUSE-3 for mechanical thrombectomy. The length of the therapeutic window is based on the diffusion weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) mismatch, core-penumbra mismatch, and clinical core mismatch paradigms. The challenges to approach unknown-onset stroke involve extending the length of the time window, the reproducibility of real-world imaging modalities, and the discovery of new methods and therapies for this condition.

Conclusion The advance in the possibilities for the treatment of ischemic stroke, while guided by imaging concepts, has become evident. New studies in this field are essential and needed to structure the health care services for this new scenario.

Resumo

Antecedentes O acidente vascular cerebral (AVC) é uma das principais causas de incapacidade em todo o mundo, e uma emergência neurológica. A trombólise intravenosa e a trombectomia mecânica são eficazes na reperfusão do parênquima em sofrimento, mas a impossibilidade de determinar o tempo exato de início era uma causa importante de exclusão ao tratamento até alguns anos atrás.

Objetivos Revisar o perfil clínico-radiológico dos pacientes com AVC de tempo indeterminado, os métodos de imagem para guiar o tratamento de reperfusão, e sugerir um protocolo para a abordagem terapêutica.

Métodos Os diferentes métodos de imagem foram agrupados de acordo com os tratamentos atuais baseados em evidências.

Resultados A maioria dos estudos não encontrou diferença entre as características clínicas e de imagem dos pacientes com AVC reconhecido ao despertar e AVC de tempo definido, o que sugere que o icto, no primeiro grupo, ocorre próximo ao acordar. Quanto ao tratamento do AVC de tempo indeterminado, quatro grandes estudos na fase três sobressaem: WAKE-UP e EXTEND para trombólise intravenosa, e DAWN e DEFUSE-3 para trombectomia mecânica. A ampliação da janela terapêutica fundamenta-se nos paradigmas de incompatibilidade da imagem ponderada de difusão–recuperação da inversão atenuada por fluidos (diffusion weighted imaging–fluid-attenuated inversion recovery, DWI-FLAIR, em inglês), do núcleo isquêmico e penumbra, e clínico-radiológico. Os desafios na abordagem do AVC de tempo indeterminado envolvem a ampliação da janela terapêutica, a reprodutibilidade das modalidades de imagem no mundo real, e a identificação de novos métodos e tratamentos para essa condição.

Conclusão É evidente o avanço nas possibilidades de tratamento do AVC isquêmico guiado pelos conceitos de imagem. Novos estudos nesse campo são essenciais, com necessidade de estruturar os serviços de saúde para esse novo cenário.

Keywords

Ischemic Stroke - Neuroimaging - Tissue Plasminogen Activator - Thrombectomy

Palavras-chave

AVC Isquêmico - Neuroimagem - Ativador de Plasminogênio Tecidual - Trombectomia

Authors' Contributions

RPL: study conception and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical review; VDBG: study conception and design, drafting of the manuscript, and critical review; FTP: study conception and design, acquisition of data, drafting of the manuscript, and critical review; RJG: study conception and design, drafting of manuscript, critical review, and final approval of the version to be published.

Publication History

Received: 13 August 2021

Accepted: 01 November 2021

Article published online:
29 December 2022

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