Transforming the management of stroke

Effective strategies for improving outcomes require efficient triage and interdisciplinary cooperation

When I commenced work as a junior neurologist, one of the first patients admitted under my care was a woman with a history of atrial fibrillation who presented acutely with a major stroke in her dominant hemisphere, causing aphasia and a dense right-sided hemiparesis. After examining the woman, I explained to her son — one of my colleagues — that the prognosis was poor; should his mother survive, she would probably be left with significant long term disability. He responded that he had just read a report in Nature about removing clots from blood vessels to reperfuse the brain during an acute stroke. The approach seemed rational, although it appeared to rest more in the realm of science fiction than something that would be of practical clinical use anytime soon.

Twenty years later, the time for intervention and clot retrieval in stroke has arrived (Box). Following a series of ground-breaking trials that have established the benefit of mechanical thrombectomy, the management of acute stroke has dramatically changed for the better. Specifically, the natural history of potentially life-threatening stroke has been completely transformed, and patients treated within the optimal time frame are now walking out of hospital with only a minimal or no deficit.

Although it has long been known that managing stroke patients in a dedicated acute stroke unit achieves better outcomes, the implementation of appropriate models of care is inconsistent, as discussed in this issue of the MJA.1,2 However, the landscape for the standard of care for acute ischaemic stroke has been significantly altered by a recent series of remarkable trials. The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) found that treating ischaemic stroke patients with endovascular thrombectomy in addition to providing standard care reduced their level of disability.3 These findings were complemented by other trials, most notably the Extending the Time for Thrombolysis in Emergency Neurological Deficits — Intra-Arterial (EXTEND-IA) trial, driven by colleagues at the Melbourne Brain Centre working together with stroke centres around Australia.4 The EXTEND-IA study investigated stroke patients with evidence of salvageable brain tissue provided by perfusion imaging within 4.5 hours of the onset of stroke. Early endovascular thrombectomy with flow restoration after intravenous alteplase (a tissue plasminogen activator) achieved better outcomes than treatment with alteplase alone. Interestingly, the release of results from the MR CLEAN trial led to the early review of EXTEND-IA data that identified the greater benefit for patients of removing clots from the proximal anterior circulation of the brain. Specifically, reperfusion of brain tissue after vessel occlusion reduced brain infarct growth, and this was associated with a greater clinical benefit for patients both in terms of brain recovery and functional outcomes.

Where do we go from here? These ground-breaking revascularisation trials have further highlighted the critical importance of time as a key determinant of stroke outcome. The lead-up to patient presentation in the acute setting — this includes patient transport, but also the effective triaging of patients between centres that do or do not offer interventional services — can seriously impede efficient treatment. Similarly, neuroimaging is crucial to any subsequent endovascular treatment, as clinical examination cannot distinguish between ischaemic and haemorrhagic stroke. Examination by a trained neurologist working as part of a multidisciplinary acute stroke team, using scales such as the National Institute of Health Stroke Scale (NIHSS), is better for correlating the clinical presentation with the site of vascular territory and therefore of blockage, enabling the most effective therapy and avoiding unnecessary intervention, and ultimately improving functional outcomes.5,6 Clinicians must also remain vigilant in their ongoing management of stroke risk factors, with clear progress best represented by the worldwide reduction in stroke mortality, more prominent in high income countries with better access to medical services and treatment.7

Determining the most effective implementation of any new treatment approach takes time, but also significantly enhances patient outcomes, particularly in the dawning era of precision medicine.8 The real challenge now is to provide the health care systems and personnel required for working through the complexities of establishing centres of neuro-interventional expertise, with appropriate patient triage that makes clot retrieval services available to everyone. The Australian and New Zealand Association of Neurologists has initiated training programs to assist registrars acquire interventional skills for managing stroke, additional to their usual neurology training. These programs will require continued dialogue with other specialties, particularly radiology and neurosurgery. As part of this process, a conjoint committee for training in interventional neuroradiology has been established to ensure that these disciplines continue to work together productively in stroke management,9 and that the standard of care continues its upward trajectory into the future, so that all Australians receive the benefits of first class stroke care.

Box – Computed tomography brain perfusion scan of a patient with stroke, having presented with acute onset of left-sided weakness*

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The scan indicates reduced mean transit time and a large area of decreased flow on the right side of the brain, and also delineates tissue at risk from potentially salvageable ischaemic brain tissue. These changes are consistent with an acute occlusion of the right internal carotid artery, for which early endovascular thrombectomy is appropriate.