DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

LGI1 and CASPR2 autoimmunity in children: Systematic literature review and report of a young girl with Morvan syndrome.

Leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) neurological autoimmunity in adults has been associated with various clinical syndromes involving central, peripheral and autonomic nervous system, while data in children is limited. We perform the first systematic literature review on paediatric LGI1 and CASPR2 autoimmunity, with focus on clinical data, in order to contribute to the definition of clinical features of LGI1 and CASPR2 autoimmunity in paediatric age and favour early diagnosis. Additionally, we report the youngest-to-date case of Morvan syndrome. We identified 37 published paediatric cases of LGI1 and/or CASPR2 autoimmunity. Most frequent syndromes were encephalitis in LGI1-positive and isolated epilepsy in CASPR2-positive children, while syndromes with predominant peripheral symptoms were most frequent in double-positive children. With the limitations imposed by the low number of cases, differences to published adult cohorts included: absence of faciobrachial dystonic seizures and hyponatremia in patients with LGI1-positive encephalitis; slightly higher proportion of isolated epilepsy syndromes in CASPR2-positive patients; absence of tumour in the whole cohort

Assessing pediatric ileocolonic Crohn's disease activity based on global MR enterography scores

Objectives This study was aimed at correlating a magnetic resonance index of activity (MaRIA) and a magnetic resonance enterography global score (MEGS) with activity indexes in a paediatric population with Crohn\u2019s disease (CD). Methods This retrospective study included 32 paediatric patients (median age 14.5 years, 18 male) with proven CD who underwent magnetic resonance enterography (MRE). A correlation analysis was performed on the MRE-based scores, the simplified endoscopic score for CD (SES-CD), the paediatric Crohn\u2019s disease activity index (PCDAI), and C-reactive protein (CRP) levels. Based on PCDAI, comparison of both global MaRIA and MEGS was made between patients with mild and moderate/severe disease activity. Results Global MaRIA correlated with SES-CD (r = 0.70, p =0.001) and PCDAI (r=0.42, p =0.016). MEGS correlated with PCDAI (r = 0.46, p = 0.007) and CRP levels (r = 0.35, p =0.046). MEGS differed significantly (p=0.027) between patients grouped by clinical disease severity. Conclusions MRE-based global scores correlated with clinical indexes of CD activity. Therefore, they represent a potential useful tool to predict CD activity and severity, as well as a possible promising alternative to endoscopy, to monitor paediatric patients with CD during their follow-up

Atypical myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and acute demyelinating polyneuropathy after SARS-CoV-2 infection: Case report and literature review

Post-infectious immune-mediated neurological complications of Sars-Cov-2 have been increasingly recognized since the novel pandemic emerged. We describe the case of a 74 years-old patient who developed a Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated unilateral retrobulbar optic neuritis a few weeks after paucisymptomatic COVID-19 disease and, subsequently, after the resolution of the optic neuritis, an acute inflammatory demyelinating polyneuropathy. So far, no cases of these two neurological manifestations have been reported in the same patient. We herein report a case characterized by both manifestations and review the accumulating literature regarding MOG antibody-associated disease following SarsCov-2 infection

Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions

Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function.

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys