Clinical impact of transoesophageal echocardiography in acute brain ischaemia: who should we select?

Funding Acknowledgements Type of funding sources: None. Background Stroke is a prevalent disease and is still the leading cause of death in Portugal. Transoesophageal echocardiography (TOE) is a sensitive test often performed to detect embolic sources. However, since its most common findings such as patent foramen ovale (PFO) and atheroma plaques do not necessarily mandate a change in treatment, there is still debate over its clinical impact in the context of brain ischaemia (BI) and which patients (pts) should be submitted to it. Purpose To assess the clinical impact of TOE following BI and to identify clinical and diagnostic testing results that could help predict which pts benefit from it. Methods A retrospective study was conducted including all pts submitted to TOE in our hospital after acute BI in 2018 and 2019. Clinical and testing data (brain, vascular and cardiac imaging and 24h-Holter monitoring) was analysed and compared between 2 groups: the pts who had findings in TOE compatible with a source of embolism which resulted in a change in treatment ("relevant TOE" group) vs all other pts who had no such findings or whose findings did not result in change in treatment ("others"). Predictors of relevant TOE were also analysed. Results Of the 87 pts (mean age of 57 and maximum of 83) included in the study, 51 (59%) had findings compatible with a potential source of embolism in TOE, PFO being the most common (n = 42). In only half of them did these findings result in a change in treatment (the relevant TOE group: n = 25; 29% of the overall population). Age and other baseline characteristics did not significantly differ between groups. Pts with a relevant TOE presented more often with visual-field defects (32% vs 10%, p = 0.020) and were more likely to have visible acute lesions on brain imaging (96% vs 76%, p = 0.032) compared with the others. There was also a borderline significant association between the presence of infarct in the territory of the superior cerebellar artery and a relevant TOE (p = 0.054). On the contrary, the presence of significant lesions in extracranial arteries was negatively associated with a relevant TOE (p = 0.016). Considering the whole population, there were no transthoracic echocardiography (TTE) predictors of a relevant TOE but when analysing only younger patients (age < 50), the presence of any abnormality in TTE became associated with a relevant TOE (OR 8.5, CI 1.1-63.9; p = 0.044). We found no predictors of relevant TOE in 24h-Holter results. Conclusions TOE commonly identified potential sources of brain embolism, which proved relevant in half the cases. In the impossibility of submitting all BI patients to TOE, this study suggests that brain and vascular imaging rather than age or other baseline characteristics may be useful in predicting a relevant result. Moreover, TTE does not seem to be an adequate screening method to select patients for TOE, except possibly in younger patients. Studies with larger samples are needed to confirm these results.

The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia

Background The role of the immune system in stroke is well-recognised. Fingolimod, an immunomodulatory agent licensed for the management of relapsing-remitting multiple sclerosis, has been shown to provide benefit in rodent models of stroke. Its mechanism of action, however, remains unclear. We hypothesised fingolimod increases the number and/or function of regulatory T cells (Treg), a lymphocyte population which promotes stroke recovery. The primary aim of this study was to rigorously investigate the effect of fingolimod on Tregs in a mouse model of brain ischaemia. The effect of fingolimod in mice with common stroke-related comorbidities (ageing and hypercholesteremia) was also investigated. Methods Young (15–17 weeks), aged C57BL/6 mice (72–73 weeks), and ApoE−/− mice fed a high-fat diet (20–21 weeks) underwent permanent electrocoagulation of the left middle cerebral artery. Mice received either saline or fingolimod (0.5 mg/kg or 1 mg/kg) at 2, 24, and 48 h post-ischaemia via intraperitoneal injection. Another cohort of young mice (8–9, 17–19 weeks) received short-term (5 days) or long-term (10 days) fingolimod (0.5 mg/kg) treatment. Flow cytometry was used to quantify Tregs in blood, spleen, and lymph nodes. Immunohistochemistry was used to quantify FoxP3+ cell infiltration into the ischaemic brain. Results Fingolimod significantly increased the frequency of Tregs within the CD4+ T cell population in blood and spleen post-ischaemia in all three mouse cohorts compared to untreated ischemic mice. The highest splenic Treg frequency in fingolimod-treated mice was observed in ApoE−/− mice (9.32 ± 1.73% vs. 7.8 ± 3.01% in young, 6.09 ± 1.64% in aged mice). The highest circulating Treg frequency was also noted in ApoE−/− mice (8.39 ± 3.26% vs. 5.43 ± 2.74% in young, 4.56 ± 1.60% in aged mice). Fingolimod significantly increased the number of FoxP3+ cells in the infarct core of all mice. The most pronounced effects were seen when mice were treated for 10 days post-ischaemia. Conclusions Fingolimod increases Treg frequency in spleen and blood post-ischaemia and enhances the number of FoxP3+ cells in the ischaemic brain. The effect of fingolimod on this regulatory cell population may underlie its neuroprotective activity and could be exploited as part of future stroke therapy.

Occipital ischaemic stroke after visual snow phenomenon – a case report

Background Persistent migraine with aura and neuroimaging examinations revealing ischaemia in the contralateral cortex may be associated with migrainous infarction. Despite being a neurological symptom that is distinct from migraine with aura, the visual snow phenomenon may also be associated with cerebral ischaemia. Here we describe a patient who reported short-lasting daily symptoms of visual snow that affected his entire visual field before becoming continuous and left-sided following acute occipital brain ischaemia. Case report In February 2017, a 74-year-old retired male was referred to our headache outpatient clinic with a diagnosis of recent right occipital cerebral ischaemia and migraine with aura. The patient reported visual snow symptoms that had changed from being bilateral and temporary to left-sided and permanent one day upon awakening; after being admitted to hospital a few hours later, he discovered he had had a stroke. He said he had never had any symptoms of migraine with aura. The visual snow phenomenon disappeared completely after about 1 year. Conclusions In our patient, a temporary daily visual snow phenomenon reversed to a persistent one. This phenomenon occurred in the part of his visual field that had been affected by the ischaemic occipital stroke, as typically happens in migrainous infarction. We hypothesise that the occipital lesion disrupted the inhibitory circuits, leading to a quadrantopic persistent visual snow. Since the mechanism may be the same as that observed in migrainous infarction, though with a different pathophysiology, it is possible to speculate that the aura in this case is the result, as opposed to the cause, of stroke in most patients.

Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?

The pandemic of Coronavirus Disease 2019 (COVID-19) presents the world with the medical challenge associated with multifactorial nature of this pathology. Indeed COVID-19 affects several organs and systems and presents diversified clinical picture. COVID-19 affects the brain in many ways including direct infection of neural cells with SARS-CoV-2, severe systemic inflammation which floods the brain with pro-inflammatory agents thus damaging nervous cells, global brain ischaemia linked to a respiratory failure, thromboembolic strokes related to increased intravascular clotting and severe psychological stress. Often the COVID-19 is manifested by neurological and neuropsychiatric symptoms that include dizziness, disturbed sleep, cognitive deficits, delirium, hallucinations and depression. All these indicate the damage to the nervous tissue which may substantially increase the incidence of neurodegenerative diseases and promote dementia.