The exact science of stroke thrombolysis and the quiet art of patient selection

Abstract

The science of metric-based patient stratification for intravenous thrombolysis, revolutionized by the landmark National Institute of Neurological Disorders and Stroke trial, has transformed acute ischaemic stroke therapy. Recanalization of an occluded artery produces tissue reperfusion that unequivocally improves outcome and function in patients with acute ischaemic stroke. Recanalization can be achieved mainly through intravenous thrombolysis, but other methods such as intra-arterial thrombolysis or mechanical thrombectomy can also be employed. Strict guidelines preclude many patients from being treated by intravenous thrombolysis due to the associated risks. The quiet art of informed patient selection by careful assessment of patient baseline factors and brain imaging could increase the number of eligible patients receiving intravenous thrombolysis. Outside of the existing eligibility criteria, patients may fall into therapeutic 'grey areas' and should be evaluated on a case by case basis. Important factors to consider include time of onset, age, and baseline blood glucose, blood pressure, stroke severity (as measured by National Institutes of Health Stroke Scale) and computer tomography changes (as measured by Alberta Stroke Programme Early Computed Tomography Score). Patients with traditional contraindications such as wake-up stroke, malignancy or dementia may have the potential to receive benefit from intravenous thrombolysis if they have favourable predictors of outcome from both clinical and imaging criteria. A proportion of patients experience complications or do not respond to intravenous thrombolysis. In these patients, other endovascular therapies or a combination of both may be used to provide benefit. Although an evidence-based approach to intravenous thrombolysis for acute ischaemic stroke is pivotal, it is imperative to examine those who might benefit outside of protocol-driven practice.

Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats

“…Stroke, which mainly causes ischemic events, is the third cause of death worldwide and the main cause of chronic, severe adult disability. The current therapy can restore cerebral blood flow within a narrow time window to prevent damage to the Bpenumbra^area, which surrounds the infarct core [40]. In order to increase the therapeutic time window, neuroprotection is an alternative or adjunct approach to thrombolysis, targeting the cerebral parenchyma in the acute ischemic phase [41].…”

Intra-arterial treatment in acute ischaemic stroke: What we learn from the MR CLEAN trial

“…1 Although IV t-PA may be effective, several factors, including the location, size, and characteristics of the thrombus, may lead to tPA resistance in about 50% of patients. 2 We already know that the chances of recanalisation with IV t-PA are even more limited in cases of proximal large artery occlusions. In a landmark study 3 it was shown that the overall chances of recanalisation with IV thrombolysis are around 30%, but less when the thrombi are in the middle cerebral artery stem (24%) or in the proximal internal carotid artery (8%).…”

Factors that influence variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke: results of a discrete choice experiment

“…16 Thrombolytic treatment may result in adverse effects, such as systemic bleeding, angioedema 17 and symptomatic intracranial haemorrhage (sICH), which is the most disabling and potentially fatal complication, occurring in approximately 3-4% of patients. 12 By definition, sICH usually results in worse disability than would have occurred without thrombolytic treatment and in a small proportion of patients can be responsible for death.…”

“…14, 17 Given the recorded variation in thrombolysis treatment rates, 19 the lack of expert consensus on several exclusion criteria for treatment (such as recent medical procedures and spontaneous improvement rate) 20 and the ongoing debates regarding the efficacy of thrombolysis, [21][22][23][24][25][26] it is important to understand factors which influence clinicians' decisions about whether or not to give intravenous thrombolysis to patients with acute ischaemic strokes, using a method that reflects decision-making in practice. 27,28 Trial evidence and guidelines on intravenous thrombolysis…”

“…Our findings indicate that factors underpinning this uncertainty in decision-making include medical factors, such as patients presenting with minor strokes, and those at the upper limit of the stroke treatment window (where there is insufficient evidence of the benefit of thrombolysis or where there may be uncertainty about the existing evidence). 17 The results also raise an important issue regarding the treatment of patients who would be deemed ineligible for treatment based on the current licensing criteria. For instance, several of the hypothetical patients described in the vignettes would be considered outside the licensing criteria and would thus be excluded from most major clinical trials (e.g.…”