Serum D-serine levels are altered in early phases of Alzheimer\u2019s disease: towards a precocious biomarker

D-Serine acts as a co-agonist of N-methyl-D-aspartate receptors (NMDAR) which appear overactivated in AD, while d-aspartate is a modulatory molecule acting on NMDAR as a second agonist. The aim of this work is to clarify whether the levels of these D-amino acids in serum are deregulated in AD, with the final goal to identify novel and precocious biomarkers in AD. Serum levels of L- and D-enantiomers of serine and aspartate were determined by HPLC using a pre-column derivatization procedure and a selective enzymatic degradation. Experimental data obtained from age-matched healthy subjects (HS) and AD patients were statistically evaluated by considering age, gender, and disease progression, and compared. Minor changes were apparent in the serum L- and D-aspartate levels in AD patients compared to HS. A positive correlation for the D-serine level and age was apparent in the AD cohort. Notably, the serum D-serine level and the D-/total serine ratio significantly increased with the progression of the disease. Gender seems to have a minor effect on the levels of all analytes tested. This work proposes that the serum D-serine level and D-/total serine ratio values as novel and valuable biomarkers for the progression of AD: the latter parameter allows to discriminate CDR 2 and CDR 1 patients from healthy (CDR 0) individuals

Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2

Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment

Age-dependent effect of susceptibility factors on the risk of intracerebral haemorrhage: Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy)

Objective To investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH). Methods We performed a case-control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1-Q4). Results We analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively). Conclusions Our findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH

Age-dependent effect of susceptibility factors on the risk of intracerebral haemorrhage: Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy)

43noObjective To investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH). Methods We performed a case-control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1-Q4). Results We analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively). Conclusions Our findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.restrictedrestrictedLocatelli M.; Grassi M.; Saba V.; Iacovello L.; Di Castelnuovo A.; De Gaetano G.; Zedde M.; Marcheselli S.; Silvestrelli G.; Ciccone A.; Delodovici M.L.; Princiotta Cariddi L.; Giossi A.; Zini A.; Paciaroni M.; Acciarresi M.; Azzini C.; De Vito A.; Gamba M.; Magoni M.; Del Sette M.; Toriello A.; Gandolfo C.; Finocchi C.; Bonifati D.M.; Tassi R.; Martini G.; Cavallini A.; Morotti A.; Bonacina S.; Mazzoleni V.; Pezzini D.; Chiti A.; Calabro R.S.; Musolino R.; La Spina P.; Grillo F.; Tomelleri G.; Lodigiani C.; Ritelli M.; Colombi M.; Padovani A.; Pezzini A.Locatelli, M.; Grassi, M.; Saba, V.; Iacovello, L.; Di Castelnuovo, A.; De Gaetano, G.; Zedde, M.; Marcheselli, S.; Silvestrelli, G.; Ciccone, A.; Delodovici, M. L.; Princiotta Cariddi, L.; Giossi, A.; Zini, A.; Paciaroni, M.; Acciarresi, M.; Azzini, C.; De Vito, A.; Gamba, M.; Magoni, M.; Del Sette, M.; Toriello, A.; Gandolfo, C.; Finocchi, C.; Bonifati, D. M.; Tassi, R.; Martini, G.; Cavallini, A.; Morotti, A.; Bonacina, S.; Mazzoleni, V.; Pezzini, D.; Chiti, A.; Calabro, R. S.; Musolino, R.; La Spina, P.; Grillo, F.; Tomelleri, G.; Lodigiani, C.; Ritelli, M.; Colombi, M.; Padovani, A.; Pezzini, A

Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy

Objective To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. Methods We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH. Results We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32). Conclusions In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH