Microvascular dysfunction in pediatric patients with SARS-COV-2 pneumonia: report of three severe cases.

The coronavirus 19 (COVID-19) pandemic has affected hundreds of millions of people worldwide: in most of cases children and young people developed asymptomatic or pauci-symptomatic clinical pictures. However authors have showed that there are some categories of childhood more vulnerable to COVID-19 infection such as newborns or children with comorbidities. We report for the first time to the best of our knowledge about microvascular dysfunction in three pediatric clinical cases who developed COVID-19 infections with need of pediatric critical care. We found that sublingual microcirculation is altered in children with severe COVID-19 infection. Our findings confirmed most of data already observed by other authors in adult population affected by severe COVID-19 infection, but with distinct characteristics than microcirculation alterations previous observed in a clinical case of MIS-C. However we cannot establish direct correlation between microcirculation analysis and clinical or laboratory parameters in our series, by our experience we have found that sublingual microcirculation analysis allow clinicians to report directly about microcirculation dysfunction in COVID-19 patients and it could be a valuable bedside technique to monitor thrombosis complication in this population.

Infection prevention in endoscopy practice: comparative evaluation of re-usable vs single-use endoscopic valves.

Re-usable air/water and suction valves used in endoscopes often demonstrate risk of infection. To the authors' knowledge, the safety and efficacy of re-usable and single-use valves have not been compared to date. As such, a laboratory investigation was undertaken to compare the safety and efficacy of re-usable and single-use valves at 11 Italian endoscopy sites. Safety was evaluated by analysing the rinse liquid of reprocessed re-usable valves ready for use, and efficacy was assessed based on the completion of endoscopic procedures without valve malfunction. This study found significantly lower contamination of single-use valves compared with re-usable valves (0 vs 29.1%, respectively; P=0.007) and similar efficacy (97.6 vs 98.8%, respectively; P=ns). Microbiological analysis of the rinse liquid of reprocessed re-usable valves identified various surviving micro-organisms and highlighted their potential pathogenicity. Such data suggest that sterile single-use valves may be safer than re-usable valves, and have comparable performance.

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency.

Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small- and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

Neonatal Developmental Venous Anomalies: Clinicoradiologic Characterization and Follow-Up.

BACKGROUND AND PURPOSE: Although developmental venous anomalies have been frequently studied in adults and occasionally in children, data regarding these entities are scarce in neonates. We aimed to characterize clinical and neuroimaging features of neonatal developmental venous anomalies and to evaluate any association between MR imaging abnormalities in their drainage territory and corresponding angioarchitectural features. MATERIALS AND METHODS: We reviewed parenchymal abnormalities and angioarchitectural features of 41 neonates with developmental venous anomalies (20 males; mean corrected age, 39.9 weeks) selected through a radiology report text search from 2135 neonates who underwent brain MR imaging between 2008 and 2019. Fetal and longitudinal MR images were also reviewed. Neurologic outcomes were collected. Statistics were performed using χ2, Fisher exact, Mann-Whitney U, or t tests corrected for multiple comparisons. RESULTS: Developmental venous anomalies were detected in 1.9% of neonatal scans. These were complicated by parenchymal/ventricular abnormalities in 15/41 cases (36.6%), improving at last follow-up in 8/10 (80%), with normal neurologic outcome in 9/14 (64.2%). Multiple collectors (P = .008) and larger collector caliber (P < .001) were significantly more frequent in complicated developmental venous anomalies. At a patient level, multiplicity (P = .002) was significantly associated with the presence of ≥1 complicated developmental venous anomaly. Retrospective fetal detection was possible in 3/11 subjects (27.2%). CONCLUSIONS: One-third of neonatal developmental venous anomalies may be complicated by parenchymal abnormalities, especially with multiple and larger collectors. Neuroimaging and neurologic outcomes were favorable in most cases, suggesting a benign, self-limited nature of these vascular anomalies. A congenital origin could be confirmed in one-quarter of cases with available fetal MR imaging.

Results of an educational campaign on stroke awareness in the 2032 Rotary District in Northern-Western Italy.

BACKGROUND: People often ignore the usefulness of stroke prevention, the typical onset symptoms, and the efficacy of the new therapies. In order to attempt to correct this situation, we performed an educational campaign addressed to Rotary club associates and their relatives or friends in the Italian Rotary District 2032. METHOD: The campaign consisted in three phases: (1) Compilation of a simple questionnaire on stroke, followed by a scientific relation on the disease, distribution of didactic materials, and organization of screening sessions on individual stroke risk evaluation; (2) Recompilation by participants of the same previous questionnaire; (3) Statistical evaluation of the improvement of stroke knowledge. RESULTS: The initial percentage of wrong answers (number of subjects 657) was 22.41% ((A) stroke general knowledge 15.45%; (B) stroke risk factors 25.65%; (C) Stroke early symptoms 22.65%). At the end of the campaign, the total percentage of wrong answers (number of subjects 296) attained the 13.18% ((A) stroke general knowledge 8.22%; (B) stroke risk factors 14.98%; (C) stroke early symptoms 13.85%). All these differences were strongly significant at the statistical analysis. DISCUSSION AND CONCLUSION: We demonstrated that our educational campaign obtained an important improvement of stroke awareness in our sample. We hope that the enhanced awareness might induce a more frequent diffusion of primary prevention strategies, an increased capacity of recognizing onset stroke symptoms with shortening of patients' presentation in the Emergency Room of the hospitals when they can undergo thrombolysis/thrombectomy.

Planning a campaign to fight stroke: an educational pilot project in La Spezia, Italy.

INTRODUCTION: Best medical treatments of ischemic stroke are admission to stroke unit, intravenous thrombolysis and, in selected cases, thrombectomy. Time from symptom onset to interventions is the best predictor of clinical outcome. In order to verify the effectiveness of an active education programme of awareness on the knowledge of stroke, we performed a local campaign "on the field". SUBJECTS AND METHODS: We selected 101 subjects from the general population who took part in the "stroke awareness campaign" organised by the Italian Association for the fight against stroke (A.L.I.Ce). Mean age was 59 years (50% female; 50% male); 55% of the sample reported a high level of education (> 8 years: high school or university degree). After a short multiple-choice questionnaire, we administered a face-to-face standard educational protocol (15 min). The efficacy of that educational intervention was then verified after a period of 12 months, by telephone interview. RESULTS: There was improvement both in the definition of stroke (66% vs. 92%, p < .001) and in recognizing symptoms and signs (19% vs. 72%, p < .001). Knowledge of the importance of stroke unit in the acute treatment of stroke did not improve, as it was already high on baseline (92% vs. 97%, p: n.s.). The improvement was evident in particular in younger and higher educated people, without difference in gender. There was no difference based on risk factor profiles of participants. CONCLUSIONS: Our results suggest that a personalised education can improve knowledge on stroke symptoms and signs, independently of gender and personal risk factors. The results should be verified in larger and less selection population.

Vein of Galen aneurysmal malformation (VGAM) in the fetus: retrospective analysis of perinatal prognostic indicators in a two-center series of 49 cases.

OBJECTIVE: Vein of Galen aneurysmal malformation (VGAM) is a rare fetal anomaly, the neurological outcome of which can be good with appropriate perinatal management. However, most fetal series are too small to allow reliable statistical assessment of potential prognostic indicators. Our aim was to assess, in a two-center series of 49 cases, the prognostic value of several prenatal variables, in order to identify possible prenatal indicators of poor outcome, in terms of mortality and cerebral disability. METHODS: This was a retrospective study involving 49 cases of VGAM diagnosed prenatally and managed at two centers over a 17-year period (1999-2015). All cases had undergone detailed prenatal cerebral and cardiac assessment by grayscale ultrasound, color and pulsed-wave Doppler and magnetic resonance imaging (MRI). Ultrasound and MRI examination reports and images were reviewed and outcome information was obtained from medical reports. Volume of the VGAM (on ultrasound and MRI) was calculated and development of straight-sinus dilatation, ventriculomegaly and other major brain abnormalities was noted. Cardiothoracic ratio, tricuspid regurgitation and reversed blood flow across the aortic isthmus were evaluated on fetal echocardiography. Major brain lesions were considered by definition to be associated with poor outcome in all cases. Pregnancy and fetoneonatal outcome were known in all cases. Fetoneonatal outcome and brain damage were considered as dependent variables in the statistical evaluation. Poor outcome was defined as death, late termination of pregnancy due to association with related severe brain anomalies or severe neurological impairment. RESULTS: At a mean follow-up time of 20 (range, 0-72) months, 36.7% of the whole series and 52.9% of the cases which did not undergo late termination were alive and free of adverse sequelae. Five (10.2%) cases showed progression of the lesion between diagnosis and delivery. On univariate analysis, dilatation of the straight sinus, VGAM volume ≥ 20 000 mm3 and tricuspid regurgitation were all significantly related to poor outcome. However, on logistic regression analysis, the only variables associated significantly with poor outcome were tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 . The former was also the only variable associated with brain damage. CONCLUSIONS: Major brain lesions, tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 are the only prenatal variables associated with poor outcome in fetal VGAM. Prenatal multidisciplinary counseling should be based on these variables. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients.

The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

Congenital neuroblastoma with symptoms of epidural compression at birth.

The occurrence of congenital neuroblastoma presenting at birth with symptoms of epidural compression secondary to spinal canal invasion is rare. Almost all cases reported in the literature have survived from the tumor but suffer severe sequelae, with the exception of the 2 most recently described whose birth was anticipated. The 3 cases of this article have been followed for a minimum of 5 years with the aim to describe their definitive late complications. In none of these cases had the routine ultrasound scan performed in third trimester of pregnancy discovered a tumor mass, nor had it shown abnormal fetal movements. All had leg hypotonia detected on the first day of life. In all, both primary and intraspinal tumors responded well to chemotherapy. All survive with motor deficit and severe bladder dysfunction despite early physiotherapy. Scoliosis has developed in the case with the longest follow-up. The description of these patients enforces the importance of early diagnosis of tumor masses in late pregnancy. Neonatologists should be aware of this rare clinical entity and take it into account in the differential diagnosis with other conditions of early-onset hypotonia. On the other hand, obstetric sonologists should be aware of the possibility to detect such rare tumors in late pregnancy, as anticipation of delivery may reduce the risk of late sequelae.

Validation of a simple method for atrial fibrillation screening in patients with stroke.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in adult and old people and represents a risk factor for stroke. Correct AF individuation bears strong relevance in primary and secondary stroke prevention. Our goal was to evaluate the reliability of a low-cost, non-invasive technology in detecting AF in acute stroke patients. AFib model BP3MQ1-2D (Microlife USA, Dunedin, FL) showed good accuracy in diagnosing AF in a general cardiologic outpatient population. We carried out an observational study in patients with recent stroke. We studied 207 subjects, 103 men, 104 women, mean age (±SD) 77.7 ± 11.34 years, who underwent a test by AFib device with indication of AF or lack of it. The golden standard was a 12-lead EKG done immediately and evaluated by a certified cardiologist. We computed estimates of Sensitivity and Specificity and their 95 % confidence intervals (CI). AF was present in 38 subjects from the sample of 207 (18.4 %). AFib correctly demonstrated AF in 34 and failed diagnosing AF in 4 cases; on the other hand, AFib correctly excluded AF in 167 and caused an erroneous diagnosis of AF in 2 cases. The Sensitivity was 0.895 (95 % CI 0.7597-0.958) and the Specificity was 0.988 (95 % CI 0.958-0.997). The AFib device global accuracy was 0.971 (95 % CI 0.938-0.987). This device was able to detect AF with high specificity and a good sensitivity. This device may be considered as an accurate tool in detecting AF in stroke patients.

Influence of vascular risk factors and neuropsychological profile on functional performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study (MILES).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease that may lead to disability and whose phenotype modulators are still unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we assessed the influence of vascular risk factors and the effect of different cognitive domains (memory, psychomotor speed and executive functions) performances on functional abilities in CADASIL in comparison with age-related leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age 50.3 ± 13.8 years, 47.1% males) and 68 ARL patients (70.6 ± 7.4 years, 58.8% males). Considering vascular risk factors, after adjustment for age, CADASIL patients had higher mean BMI values than ARL patients. Stroke history frequency was similar in the two groups. After adjustment for age, more CADASIL patients were disabled (impaired on ≥ 2 items of the Instrumental Activities of Daily Living scale) in comparison with ARL patients, and CADASIL patients had worse functional performances evaluated with the Disability Assessment for Dementia (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and disability. The cognitive profile of CADASIL and ARL patients was similar, but on a stepwise linear regression analysis functional performances were mainly associated with the memory index (ß = -0.418, P < 0.003) in CADASIL patients and the executive function index (ß = -0.321, P = 0.028) in ARL. CONCLUSIONS: This study suggests that hypertension may contribute to functional impairment in CADASIL and that memory impairment has a large influence on functional decline in contrast with that observed in a sample of subjects with ARL.

Incidence and predictors of acute symptomatic seizures after stroke.

OBJECTIVE: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. METHODS: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (≤7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. RESULTS: A total of 714 patients (315 women, 399 men; age 27-97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5-14.9) followed by CIHT (OR 2.7; 95% CI 0.8-9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8-20.8) and for CI (OR 3.1; 95% CI 1.3-7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03-0.8) was a protective factor for IPH. CONCLUSION: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke.

Fabry disease in patients with migraine with aura.

Anderson-Fabry disease (AFD) is an X-linked recessive lysosomal disease caused by alpha-galactosidase A (alpha-gal) deficiency, causing progressive glycosphingolipid storage in various organ systems. Headache is a frequent symptom. Cerebral magnetic resonance imaging (MRI) often shows multiple white matter lesions (WML), like those seen in patients affected by migraine, in particular with aura (MA). To our knowledge, there are no reports about the prevalence of AFD in patients with MA. The objective of the study was to determine AFD prevalence, as assessed by alpha-gal activity and genetic tests, in MA patients. We evaluated 73 consecutive patients followed by the Headache Centre of our Department with a diagnosis of MA. They were screened for migraine characteristics and cerebrovascular risk factors. Gaseous contrast transcranial Doppler was used to diagnose right-to-left shunt and MRI to detect WML. All patients underwent blood test to evaluate peripheral alpha-gal activity and to identify alpha-gal gene mutations. Of 73 consecutive screened subjects (59 females, 14 males; mean age 38.3 +/- 11.8 years), the known GLA pathologic mutation p.[Asp313Tyr] was found in a 38-year-old woman, with a history of MA, deep venous thrombosis and abdominal pain. Cerebral MRI showed small WML. This is the first study reporting AFD prevalence in a cohort of MA patients. We found a relatively high prevalence (about 1.37%) among the examined patients, even if this finding needs to be confirmed in a larger sample. Despite this high prevalence, it seems not necessary to screen systematically all MA patients for AFD, but since it is a treatable genetic disorder, it is worthwhile to consider it for the subgroup of patients presenting WML and other typical AFD symptoms.

Neuroradiology of chemotherapeutic. Neurotoxicity in children.

Hemolymphoproliferative diseases and brain tumors are among the most common causes of morbidity and mortality in children. In the past few years, increased effectiveness of treatment modalities has significantly increased overall survival, but has also disclosed new aspects of the natural history of these disorders, among which central nervous system involvement due to iatrogenic side-effects. Magnetic resonance imaging plays an important, often crucial, role in the diagnosis of several of these disorders. Close interdisciplinary collaboration between hemato-oncologists and neuroradiologists is of paramount importance to provide affected children with an early diagnosis and proper treatment.

Long-term follow-up of neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome.

OBJECTIVE: The aim of this study is to describe the long-term neurological, neuropsychological and neuroradiological sequelae and to determine prognostic factors for neurological outcome in children with neuroblastoma-associated opsoclonus-myoclonus-ataxia (OMA) syndrome. METHODS: Data on medical history were collected for the study patients. Examinations with grading of neurological signs, neuropsychological tests and brain magnetic resonance imaging with spectroscopy were performed during a follow-up clinic. RESULTS: Fourteen subjects entered the study. All had localized neuroblastoma and they were evaluated after a median of 7.8 years. Patients with a chronic/multiphasic neurological course received steroids combined with intravenous immunoglobulins in the majority of cases. 71% presented neurological sequelae and 62% had a full-scale IQ below the normal range. All patients showed at least some deficit in the neuropsychological functions assessed (language, visual-motor integration, memory, attention and motor ability). Long-term deficits were more frequently detected in patients with an interval of more than 2 months between OMA onset and its diagnosis, even if in most comparisons statistical significance was not reached. Cerebellar atrophy, observed in 36% of patients, was not associated with the neurological outcome. CONCLUSIONS: Persisting disability is present in most children with neuroblastoma-associated OMA. However, our results support the role of an early diagnosis of OMA in reducing sequelae and encourage the use of new immunosuppressive therapies.

[Neurologic emergency in children's hospital. Stroke]. / Emergenza neurologica in pediatria: lo stroke.

AIM: The results may be related to the relative delay in diagnosis and thus in treatment. The authors hope that their paper will help make physicians who work in emergency rooms more aware of the increase in stroke in children. METHODS AND RESULTS: The study a departmental study in the Children's Hospital, carried out at the Giannina Gasslini Children's Hospital of Genoa, Italy. The authors report on 23 children with stroke who were admitted at onset to the pediatric emergency department. The incidence of patients with stroke at the Institute between 2001 and 2005, was 0.8% among neurology patients and 0.02% among all pediatric patients. This incidence would appear to be lower than the rates reported in the literature. This is most likely due to the fact that patients who presented at the Emergency Department at onset of the stroke were not taken in consideration. In the last few years, children with stroke have been treated empirically by anticoagulant or antiplatelet therapy. Patients with sickle cell disease, with venous stroke, or with heart disease are all treated in a rather homogeneous manner. CONCLUSIONS: These cases represent the different types of presentation of stroke in children and also clearly display the different therapeutic strategies that have been applied. In fact, the patients were treated on the basis of an individual protocol which was decided case by case but a critical review of these cases establishes a necessary multidisciplinary protocol.

In vivo neuroprotection by a creatine-derived compound: phosphocreatine-Mg-complex acetate.

Phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) is a creatine-derived compound that in previous in vitro research was able to increase neuronal creatine independently of the creatine transporter, thus providing hope to cure the hereditary syndrome of creatine transporter deficiency. In previous research we showed that it reproduces in vitro the known neuroprotective effect of creatine against anoxic damage. In the present paper we investigated if PCr-Mg-CPLX reproduces this neuroprotective effect in vivo, too. We used a mouse model of transient middle cerebral artery occlusion. Mice received PCr-Mg-CPLX or a mixture of the two separate compounds phosphocreatine (PCr) and MgSO(4), or vehicle. The injections were done 60 min and 30 min before ischemia. Forty-eight hours after ischemia neurological damage was evaluated with Clark's behavioural tests, then the infarct volume was measured. PCr-Mg-CPLX reduced the infarct volume by 48%, an effect that was not duplicated by the separate administration of PCr and MgSO(4) and the neurological damage was decreased in a statistically significant way. We conclude that PCr-Mg-CPLX affords in vivo neuroprotection when administered before ischemia. These results are comparable to previous research on creatine administration in experimental stroke. PCr-Mg-CPLX maintains creatine-like neuroprotective effects in vivo as well as in vitro. Our study suggests that PCr-Mg-CPLX might have a therapeutic role in the treatment of hereditary creatine transporter deficiency and of conditions where there is a high risk of impending stroke or cerebral ischemic damage, like high-risk transient ischemic attacks, open heart surgery, and carotid surgery.