COVID-19 and Stroke: Casual or Causal Role?

BACKGROUND: The COVID-19 outbreak is currently the major public health concern worldwide. This infection, caused by the novel coronavirus Sars Cov2, primarily affects respiratory system, but there is increasing evidence of neurologic involvement and cerebrovascular accidents. CASE REPORT: We present a case of stroke in a 62-year-old COVID-19-positive patient, with multiple vascular risk factors. The patient arrived 1 h after onset of symptoms, was treated with recombinant tissue plasminogen activator (rtPA) with improvement of neurologic deficits, and later developed right foot arterial ischemia (recanalized by balloon catheter angioplasty) and left arm superficial venous thrombosis. A control computed tomography (CT) scan 7 days after onset showed hemorrhagic transformation of ischemic lesion without mass effect. However, respiratory and neurologic conditions improved so that the patient was discharged to rehabilitation. DISCUSSION: Until now, few cases of stroke in COVID-19 have been described, mainly in severe forms. This patient had ischemic injuries in different sites as well as venous thrombosis; hence, we speculate that Sars Cov2 could have a direct role in promoting vascular accidents since its receptor ACE2 is a surface protein also expressed by endothelial cells. This case suggests that COVID-19 can favor strokes and in general vascular complications, even in milder cases, and the presence of preexisting risk factors could play a determinant role.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T.

The objective of this study is to report a new manifestation of acute stroke following antifibrinolytic agent administration in young women carrying heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study included two young women who developed an acute ischaemic stroke following three days of tranexamic acid administration for bleeding gynaecological disorders. Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto-temporal lesion due to subocclusion of the right middle cerebral artery. Case 2, a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed left capsular and periventricular infarcts due to near occlusion of the left internal carotid artery. Thrombophilia screening, coagulation parameters, homocysteine testing, 12-lead electrocardiography, and transthoracic and transoesophageal echocardiography were unremarkable. Genetic assay showed that both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is replaced by thymidine (T) at base position 677. To our knowledge, this is the first report describing the association between genetic factors and the onset of stroke following antifibrinolytic drugs intake. These data suggest a synergic effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on the pathogenetic mechanisms leading to ischaemic stroke in young people.