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‘Time is brain’: Decisions prior to administering thrombolytics

Article-‘Time is brain’: Decisions prior to administering thrombolytics

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A look at the acute management of ischemic stroke updates with advanced reperfusion strategies.

Stroke is the leading cause of long-term disability in developed countries and one of the top causes of mortality worldwide. The past decade has seen substantial advances in the diagnostic and treatment options available to minimise the impact of acute ischemic stroke.  

The incidence and prevalence of stroke in the Middle East (ME) have increased drastically in the last decade exceeding that of developed countries. A systematic review has found that the incidence rate of stroke in Middle Eastern countries is 22.7 to 250 out of 100,000 population per year between 2000 and 2014. 

RAK Hospital recently carried out a retrospective review of the data from 70 consecutive patient records admitted between April 2014 and August 2019 with a clinically confirmed diagnosis of stroke by magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), or computed tomography (CT-scan). The mean age of the patients was 55 ± 10 years with male predominance. The frequency of strokes was high in the age group of 40 to 59 years. Around 41.18 per cent of total strokes were ischemic while 2.94 per cent of patients suffered a haemorrhagic stroke.  

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Dr. Sweta Adatia, Specialist Neurologist and Medical Director at RAK Hospital, UAE

Hypertension (28.3 per cent), smoking (25 per cent), and diabetes mellitus (17.5 per cent) were common risk factors associated with stroke. RAK Hospital currently has a stroke code in place that helps all people be aware of the urgency in assessing patients with acute ischemic or haemorrhagic stroke.  

Simple tools, such as NIHSS scoring, assists in the evaluation of the stroke and it is necessary to provide training to the junior doctors that assess the emergency for such scores. It is also important to monitor the progress by checking the modified Rankin scales. It is prudent to have availability of round-the-clock CT scanners or MRI if one is having a stroke programme. Equally necessary is the training of the physiotherapy staff for effective rehabilitation following the stroke, which should begin while the patient is at the hospital. 

Reperfusion therapy is the Holy Grail in treatment of the ischemic strokes, however, ‘time is brain’. The choice of the right imaging procedures is crucial for taking the decision. The time to administration of the thrombolytic and the availability of the mechanical thrombectomy decides the outcomes in acute stroke patients.  

The immediate goal of reperfusion therapy for acute ischemic stroke is to restore blood flow to the regions of the brain that are ischemic but not yet infarcted. The long-term goal is to improve outcomes by reducing stroke-related disability and mortality.  

‘Time is Brain’ reminds us that stroke is an emergency. However, the tissue window has taught us that the treatment time window still exists in late presenters. We should not give up easily and do our best in identifying the penumbra. While the time window is based on the witnessed time of a stroke event that takes place, the tissue window is the biological timing of evolving ischemia.  

Brain ischemia is a dynamic process. Each patient may tolerate the ischemia differently because of the difference in cerebral reserve, collateral circulation, size and time of an infarction. With the advent of new CT and MRI technology, we are now capable of accurately assessing such processes. 

Advanced imaging can play a crucial role in identifying patients that could benefit from endovascular intervention presenting within extended treatment time windows. A patient presenting within six hours of stroke symptom onset typically should be evaluated with non-contrast CT and CT angiogram (CTA), which could be sufficient for patient selection for thrombectomy as shown in a multicenter randomised clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands (MRCLEAN) 

Newer trials such as DWI or CTP assessment with a clinical mismatch in the triage of wake-up and late presenting strokes undergoing neurointervention with Trevo (DAWN) and endovascular therapy, following imaging evaluation for ischemic stroke 3 (DEFUSE 3), extended this time window even further. This demonstrates the benefit of endovascular thrombectomy for patients up to 24 hours following symptom onset. The imaging can identify patients with large diffusion/perfusion mismatches in whom treatment beyond the conventional six-hour treatment window can also benefit. 

The salvage ability of brain tissue largely depends on the degree of collateral perfusion of the ischemic territory. Individual patient variability in diffusion/perfusion mismatch volume on advanced imaging will direct subsequent treatment. Given this new data, the clinician and radiologist should be prepared to screen and administer thrombolytic or endovascular therapy within 24 hours of stroke onset. Time is a surrogate for stroke viability. For the high-risk group presenting from six hours to 24 hours after onset, however, accurate determination of core and viable tissue is critical.  

Recently, two published clinical trials used MRI mismatch rather than CT perfusion mismatch to guide the use of IV tPA up to patients with AIS between six and 12 hours of onset, and the outcome was positive. Both MRI-guided thrombolysis for stroke with unknown time of onset (WAKE-UP) and IV alteplase in MR-selected patients with stroke of unknown onset (MR WITNESS) trials used MRI diffusion-weighted image/fluid-attenuated inversion recovery (DWI/FLAIR) to look for the mismatch rather than a perfusion scan. 

While multiple parameters need to be considered when deciding when a patient should receive reperfusion treatment, the most important factors include the time window between symptom onset and the presentation and imaging-based assessment of perfusion collateral flow. If the patient has a proximal vessel occlusion on CTA, no intracranial haemorrhage and an Alberta stroke programme early CT score (ASPECT) score of >6, he or she may benefit from intra-arterial (IA) therapy. If available, CTP and MRI can be useful. Magnetic resonance imaging is the most sensitive and specific imaging modality for determination of infarct core and viable penumbral tissue.  

In the near future, artificial intelligence may help assess the presence of a penumbra faster and with more precision. Already many such automated software cloud-based programs are available, which assist the physician in making an informed decision.  


References available on request. 


Dr. Sweta Adatia, MBBS, MD, DNB, FACP, MBA, is a Specialist Neurologist and Medical Director at RAK Hospital, UAE. She is speaking at the Internal Medicine conference at Arab Health 2023. 

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