by Benedetta Bodini
This very interesting symposium on New evidence to tackle major health issues in stroke was organised in cooperation with the European Stroke Organisation. It started with a lecture by Prof. Georgios Tsivgoulis who discussed the relevance of detecting atrial fibrillation to prevent stroke. He started by indicating that, among all the causes of ischaemic stroke, the cardioembolic cause represents a major component. However, he underlined that an indiscriminate anticoagulation of all embolic strokes of undetermined source (ESUS) is not supported by randomised controlled trials comparing the use of oral anticoagulants with aspirin in this type of patients. Moreover, indiscriminate anticoagulation in these patients results in very high costs due to an increased number of bleeding events in patients treated with oral anticoagulants. Indeed, we have to consider that ESUS is a heterogeneous group of cerebrovascular disorders with multiple etiologies of cerebral embolism. Implantable cardiac monitoring has been shown to be able to detect atrial fibrillation only in a minority of patients with ESUS, with a key predictor of eventually finding atrial fibrillation being the increased duration of monitoring. Interestingly, subclinical device-detected atrial fibrillation has been shown to have the potential to predict clinical atrial fibrillation and increased stroke risk. Tsivgoulis then examined the different methods to monitor cardiac rhythm in individuals with stroke risk factors and indicated that there is clear evidence suggesting that the diagnostic yield increases with duration, dispersion and number of screenings, although all strategies (including serial 30-days Holter monitoring) have low yield comparable with the implantable cardiac monitoring. In a recent study, Tsivouglis’s team found that paroxysmal atrial fibrillation detection was higher in the cohort with implantable cardiac monitoring compared with the group with traditional Holter monitoring. Patients with implantable cardiac monitoring were also found to have significantly higher rates of anticoagulation initiation and lower risk of stroke recurrence during follow-up. These results were confirmed in a large meta-analysis recently published in Neurology (Tsivgoulis et al, 2022). He then indicated that even atrial fibrillation detected after stroke (both the cardiogenic and the neurogenic variant) is associated with a significant increase in the risk of recurrent stroke and death. Overall, the international recommendations indicate that in stroke patients, additional cardiac rhythm monitoring by long-term non-invasive ECG monitors or implantable loop recorders should be employed to document silent atrial fibrillation. Moreover, in patients with cryptogenic stroke (particularly in elderly patients, with cardiovascular risk factors or comorbidities, indices of left atrial remodeling, high C2HEST score), implantation of a cardiac monitor is reasonable to optimise detection of silent atrial fibrillation.
In the second lecture of the session, Prof. Hugh Marcus discussed the treatment of vascular risk to prevent dementia. He started by indicating that dementia incidence is declining over time and there could be a relationship with a similar decline over time of cardiovascular diseases. Vascular risk factors may increase the risk of Alzheimer’s disease by the impact of vascular damage in reducing brain resources or through a direct effect on Alzheimer’s disease pathology. Epidemiological studies clearly suggest that cardiovascular risk factors, particularly in middle-aged people, significantly increase the risk of Alzheimer’s disease. Moreover, prospective studies and randomised controlled studies have shown that effectively treating hypertension reduces the risk of developing cognitive deficits and Alzheimer’s disease. Marcus then indicated that the evidence is less clear on the impact of controlling diabetes and cholesterol levels on the evolution of cognition over time. In the final part of his lecture, he discussed the important question of whether atrial fibrillation is associated with dementia. Indeed, atrial fibrillation may be involved in the pathogenesis of dementia through the induction of a thrombotic state, but also through different mechanisms, such as inflammation and hypoperfusion. A recent meta-analysis has clearly indicated that atrial fibrillation is a risk factor for cognitive impairment, and that effective control of atrial fibrillation results in a significant reduction of the risk of dementia.
The third lecture, which was focused on the treatment of asymptomatic carotid artery stenosis was presented by Prof. Allison Hallidays. She started with a reminder that worldwide more than one million strokes per year result from carotid disease. This includes carotid plaques with arteriogenic emboli and flow reducing carotid stenosis. In asymptomatic patients, multiple clinical trials have consistently shown that carotid endarterectomy significantly reduces the risk of any type of first stroke (both ipsilateral and contralateral) compared with medical treatment (blood pressure lowering, anti-thrombotic, and statin treatments). In 2019, a preplanned pooled analysis compared stenting with endarterectomy in a group of symptomatic patients, and found that the risk of stroke following the two procedures was almost identical. Several studies have compared these two procedures in asymptomatic patients. Multiple studies did not find any clear evidence supporting the superiority of stenting or surgery in preventing stroke. The recent ACST-2 trial confirmed a 1% 30-day risk in each group of procedural death or disabling stroke and a 2.5% five-year risk in each group of non-procedural disabling or fatal strokes. However, with stenting, there was a 1-2% excess risk of non-disabling strokes. Medical therapy for asymptomatic patients includes high blood pressure control (with an objective to lower blood pressure < 140/80 and maybe 120 systolic) and antithrombotic treatment with low-dose aspirin and dipyridamole or clopidogrel or possibly dipyridamole monotherapy (200 mg twice daily) if patients are intolerant or allergic to both aspirin and clopidogrel. As far as cholesterol level control is concerned, carotid guidelines suggest an LDL-cholesterol target of < 1.8 mmol/L, obtained with statins or PCSK9 inhibitors.
In the final lecture of the session, Prof. Jesse Dawson discussed the role of neuromodulation in post stroke recovery. There are several mechanisms that lead to functional impairment after stroke, including neuronal cell death, altered neuronal connectivity and secondary degeneration, and each of these mechanisms could be potentially addressed to improve functional recovery. Neuromodulation is defined as the alteration of nerve activity through targeting delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body. Methods of neurostimulation include repetitive stimulation, paired stimulation and closed loop stimulation. Most studies have looked at the use of neuromodulation to improve motor impairment, but several progresses have been made in using this approach to treat spasticity, dysphagia and to increase collateral blood flow. A recent study explored the effects of vagus nerve stimulation (VNS) on patients with stroke and found that the VNS group already had a significant clinical improvement one day after the stroke, which was maintained three months afterwards (Dawson et al, Lancet 2021). Following this study, the FDA has approved this approach to treat moderate to severe upper extremity motor deficits associated with chronic ischaemic strokes. As far as sphenopalatine ganglion stimulation is concerned, Dawson presented the results of a study (Bornstein et al, Lancet 2019) which demonstrated that this approach is safe for patients with acute ischaemic stroke and is likely to improve functional outcome. He concluded his lecture saying that neuromodulation techniques allow a degree of precision and timing which cannot be achieved by drugs and that these techniques have already begun to show success in pivotal trials.