Abstract Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4–6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012–2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Several lines of evidence support a role for brain-derived neurotrophic factor (BDNF) alterations in the etiology of eating disorders (EDs). BDNF heterozygous knockout mice show alterations in eating behavior, increased body weight and adipocyte hypertrophy. BDNF also regulates the synaptic efficiency through the modulation of key neurotransmitter systems previously known to be involved in ED. These findings, together with the fact that this neurotrophin is expressed in the hypothalamus nuclei associated with weight regulation and feeding control, led us to propose BDNF as a candidate gene for ED. To investigate the possible involvement of this neurotrophin in eating behavior, we screened the BDNF gene in 95 ED patients and identified four sequence variants. Two of them, À374A/T and À256G/A, were found in two patients with anorexia nervosa (AN) and consisted of single-nucleotide mutations within the 5 0 untranslated region (5 0 UTR). The other two polymorphisms resulted in a C to T transition located at the 5 0 UTR of the BDNF gene and an amino-acid substitution within the BDNF precursor protein (Val66Met). We performed a case-control study for these two Single-nucleotide polymorphisms in a sample of 143 ED patients and 112 unrelated controls and found a strong association of restricting AN (ANR) with the Met allele of the Val66Met BDNF polymorphism (2p ¼ 0.002). There was also evidence for a significant effect of this sequence variant on the minimum body mass index (MBMI) (2p ¼ 0.006). These results suggest that the BDNF Met66 variant may be a susceptibility factor to ED, mainly to ANR and low MBMI. Keywords: anorexia; bulimia; brain-derived neurotrophic factor; BDNF; single-nucleotide polymorphism Eating disorders (EDs) are complex and multifactorial, with the involvement of both psychosocial and biological factors. 1-6 A genetic contribution in ED is widely accepted 6-9 and genes involved in eating behavior, weight regulation, satiety and metabolism, as well as those under hormonal control are considered candidate genes for their role in anorexia nervosa (AN) and bulimia nervosa (BN). Among these candidates, we propose brain-derived neurotrophic factor (BDNF), which encodes for a neurotrophic factor with an essential role in neuronal survival and differentiation, and is also involved in synaptic efficiency and neuronal plasticity. 10-13 BDNF maps to 11p13-p14 14 and, although the structure of the coding exon is well known, 15 the genomic organization of the 5 0 noncoding exons has not been described.Several lines of evidence indicate a role of this neurotrophin in eating behavior and suggest that alterations in its function or expression pattern could be considered susceptibility factors to ED. To test this hypothesis we have characterized the genomic structure of the human BDNF gene. BDNF is composed of, at least, four 5 0 nontranslated exons and a single 3 0 coding exon (exon 5; Figure 1b). Since mRNA transcripts were different at their 5 0 ends, we determined the existence of four 5 0 untranslated exons th...

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BACKGROUND AND PURPOSE:The aim of this study was to report the CT evolution and clinical significance of HCA after intra-arterial mechanical thrombectomy (revascularization by using retrievers and/or other mechanical devices without concomitant delivery of intra-arterial thrombolytics) in our patients. These lesions are common after intra-arterial thrombolysis, being considered a negative prognostic sign. Their significance after pure mechanical thrombectomy remains unknown.

Background and Purpose-Futile recanalization after acute ischemic stroke occurs in almost half of the patients despite optimal angiographic results. Multimodal neuroimaging may help to improve patient's selection but is still dismissed by many interventionalists. Our aim was to evaluate the accuracy of each parameter of multimodal computed tomography (CT) and their combination for predicting futile recanalization after successful thrombectomy. Methods-We retrospectively reviewed a cohort of consecutive patients with anterior circulation stroke, fully assessable multimodal CT, and successful recanalization. Nonenhanced CT, CT angiography source images, cerebral blood volume (CBV), cerebral blood flow (CBF), and mismatch CBV-CBF maps were studied by Alberta Stroke Program Early CT Score (ASPECTS); collaterals on CT angiography were graded as poor or good (≤50% or >50% of the middle cerebral artery territory). Futile recanalization was defined as modified Rankin Scale score >2 at 3 months despite successful recanalization. Results-One hundred fifty patients were included and 57% of them had futile recanalization. They had lower ASPECTS on nonenhanced CT, CT angiography source images, CBV, CBF, and mismatch CBV-CBF and presented more frequently poor collaterals (all P<0.001). Among them, CBV showed the highest area under the curve (0.83; 95% confidence interval, 0.76-0.88). In multivariate analyses, CT angiography source images ≤5 (odds ratio, 5.1; 95% confidence interval, 1.2-21.9), CBV≤6 (odds ratio, 3.5; 95% confidence interval, 1.2-9.7), and poor collaterals (odds ratio, 8.6; 95% confidence interval, 1.8-41.7) were independent predictors of futile recanalization. A combined score of these 3 parameters added complementary information: 57% of the patients with score-1, 89% with score-2, and 100% with score-3 had futile recanalization. Reclassification analyses indicated that this score improved prediction of futile recanalization. Conclusions-In this population, a combined multimodal CT score predicted futile recanalization.

Background: With approximately 10% of pregnant women prescribed antidepressant drugs for the treatment of depressive disorders, there is growing concern regarding the potential long-term effects of this exposure on offspring. Research is needed in clinically relevant models to determine the effects on offspring behaviour and associated neurobiological systems. Aim: The aim of this study was to determine the effects of maternal fluoxetine treatment on anxiety-like and depressive-like behaviours in adolescent offspring as well as associated glutamatergic markers, using a clinically relevant rodent model of depression. Methods: Wistar-Kyoto (model of innate depression) and Sprague-Dawley rats were treated with fluoxetine (10 mg/kg) from gestational day 0 to postnatal day 14. Male offspring underwent behavioural testing (open field, elevated plus maze, forced swim test) at adolescence followed by quantitative immuno-detection of glutamatergic markers in the prefrontal cortex and ventral hippocampus. Results: Perinatal fluoxetine exposure exacerbated the anxiety-like and depressive-like phenotype in Wistar-Kyoto offspring and induced an anxiety-like and depressive-like phenotype in Sprague-Dawley offspring. Wistar-Kyoto offspring showed reductions in NMDA receptor NR1, NR2A and NR2B subunits, as well as post-synaptic density 95 (PSD-95) and metabotropic glutamate receptor subtype 1 (mGluR1) in the prefrontal cortex; perinatal fluoxetine exposure further reduced NR1, NR2A, PSD-95 and mGluR1 expression in Wistar-Kyoto as well as Sprague-Dawley offspring. In the ventral hippocampus perinatal fluoxetine exposure reduced PSD-95 and increased metabotropic glutamate receptor subtype 5 (mGluR5) and Homer1b/c in both Sprague-Dawley and Wistar-Kyoto strains. Conclusion: These findings suggest that maternal fluoxetine treatment exacerbates effects of underlying maternal depression on offspring behaviour, which may be mediated through alterations in the glutamatergic system. Further research investigating how to minimise these effects, whilst ensuring optimal treatment for mothers, is essential to move the field forward.

In our series, systematic histopathological and bacteriological study of the MT samples allowed a higher proportion of SE diagnosis in comparison with previous reports.

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