Publications by authors named "Daniele Marcotulli"

9 Publications

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A nationwide study on Sydenham's chorea: Clinical features, treatment and prognostic factors.

Eur J Paediatr Neurol 2021 Nov 6;36:1-6. Epub 2021 Nov 6.

Pediatric Rheumatology, Pediatric University Department, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

Objectives: Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC.

Study Design: We retrospectively analyzed the medical records of patients <18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis.

Results: We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045).

Conclusions: Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options.
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http://dx.doi.org/10.1016/j.ejpn.2021.11.002DOI Listing
November 2021

Impact of the COVID-19 Pandemic on Child and Adolescent Psychiatric Emergencies.

J Clin Psychiatry 2021 04 6;82(3). Epub 2021 Apr 6.

Department of Public Health and Pediatric Sciences, Section of Child and Adolescent Neuropsychiatry, University of Turin, Turin, Italy.

Objective: By forcing closure of schools, curtailing outpatient services, and imposing strict social distancing, the COVID-19 pandemic has abruptly affected the daily life of millions worldwide, with still unclear consequences for mental health. This study aimed to evaluate if and how child and adolescent psychiatric visits to hospital emergency departments (EDs) changed during the pandemic lockdown, which started in Italy on February 24, 2020.

Methods: We examined all ED visits by patients under 18 years of age in the 7 weeks prior to February 24, 2020, and in the subsequent 8 weeks of COVID-19 lockdown at two urban university hospitals, in Turin and Rome, Italy. ED visits during the corresponding periods of 2019 served as a comparison using Poisson regression modeling. The clinician's decision to hospitalize or discharge home the patient after the ED visit was examined as an index of clinical severity.

Results: During the COVID-19 lockdown, there was a 72.0% decrease in the number of all pediatric ED visits (3,395) compared with the corresponding period in 2019 (12,128), with a 46.2% decrease in psychiatric visits (50 vs 93). The mean age of psychiatric patients was higher in the COVID-19 period (15.7 vs 14.1 years). No significant changes were found in hospitalization rate or in the prevalence distribution of the primary reason for the psychiatric ED visit (suicidality, anxiety/mood disorders, agitation).

Conclusions: In the first 8 weeks of the COVID-19-induced social lockdown, the number of child and adolescent psychiatric ED visits significantly decreased, with an increase in patient age. This decrease does not appear to be explained by severity-driven self-selection and might be due to a reduction in psychiatric emergencies or to the implementation of alternative ways of managing acute psychopathology.
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http://dx.doi.org/10.4088/JCP.20m13467DOI Listing
April 2021

Psychological Impact of the COVID-19 Pandemic on Adults and Their Children in Italy.

Front Psychiatry 2021 12;12:572997. Epub 2021 Mar 12.

Section of Child and Adolescent Neuropsychiatry, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.

The coronavirus disease 2019 (COVID-19) pandemic has abruptly changed the life of millions as travel and social contacts have been severely restricted. We assessed the psychological impact of COVID-19 on adults and children, with special attention to health care workers (HCWs). A self-rated online survey, including the Impact of Event Scale-Revised (IES-R) for adults and the Children Revised Impact of Event Scale-Revised-13 items (CRIES-13) for their 8-18-year-old offspring, was conducted in Italy on March 20-26, 2020. Linear mixed-effects models were applied to the data, accounting for age, sex, education, and other demographic characteristics. Data were available from 2,419 adults (78.4% females, mean age 38.1 ± SD 13.1 years; 15.7% HCW) and 786 children (50.1% male, mean age 12.3 ± 3.2 years). Median (IQR) IES-R score was 30.0 (21.0-40.0), corresponding to mild psychological impact, with 33.2% reporting severe psychological impact. IES-R was lower in HCWs (29.0) than non-HCWs (31.0), but HCWs directly involved in COVID-19 care had higher scores [33.0 (26.0-43.2)] than uninvolved HCWs [28.0 (19.0-36.0)]. Median CRIES-13 score was [21.0 (11.0-32.0)], with 30.9% of the children at high risk for post-traumatic stress disorder. Parent and child scores were correlated. Up to 30% of adult and children in the pandemic area are at high risk for post-traumatic stress disturbances. The risk is greater for HCWs directly involved in COVID-19 care and for their children.
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http://dx.doi.org/10.3389/fpsyt.2021.572997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994767PMC
March 2021

Where have the children with epilepsy gone? An observational study of seizure-related accesses to emergency department at the time of COVID-19.

Seizure 2020 Dec 5;83:38-40. Epub 2020 Oct 5.

Department of Public Health and Pediatric Sciences, Section of Child and Adolescent Neuropsychiatry, University of Turin, Piazza Polonia 94, 10100, Turin, Italy.

Purpose: The COVID-19 pandemic and related lockdown measures drastically changed health care and emergency services utilization. This study evaluated trends in emergency department (ED) access for seizure-related reasons in the first 8 weeks of lockdown in Italy.

Methods: All ED accesses of children (<14 years of age) at two university hospitals, in Turin and Rome, Italy, between January 6, 2020 and April 21, 2020, were examined and compared with the corresponding periods of 2019.

Results: During the COVID-19 lockdown period (February 23-April 21, 2020), there was a 72 % decrease in all pediatric ED accesses over the corresponding 2019 period (n = 3,395 vs n = 12,128), with a 38 % decrease in seizure-related accesses (n = 41 vs n = 66). The observed decrease of seizure-related ED accesses was not accompanied by significant changes in age, sex, type of seizure, or hospitalization rate after the ED visit.

Conclusion: The COVID-19 lockdown was accompanied by a sudden decrease in seizure-related hospital emergency visits. School closure, social distancing, reduced risk of infection, and increased parental supervision are some of the factors that might have contributed to the finding.
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http://dx.doi.org/10.1016/j.seizure.2020.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534601PMC
December 2020

Neuromodulatory Action of Picomolar Extracellular Aβ42 Oligomers on Presynaptic and Postsynaptic Mechanisms Underlying Synaptic Function and Memory.

J Neurosci 2019 07 24;39(30):5986-6000. Epub 2019 May 24.

Department Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy,

Failure of anti-amyloid-β peptide (Aβ) therapies against Alzheimer's disease (AD), a neurodegenerative disorder characterized by high amounts of the peptide in the brain, raised the question of the physiological role of Aβ released at low concentrations in the healthy brain. To address this question, we studied the presynaptic and postsynaptic mechanisms underlying the neuromodulatory action of picomolar amounts of oligomeric Aβ (oAβ) on synaptic glutamatergic function in male and female mice. We found that 200 pm oAβ induces an increase of frequency of miniature EPSCs and a decrease of paired pulse facilitation, associated with an increase in docked vesicle number, indicating that it augments neurotransmitter release at presynaptic level. oAβ also produced postsynaptic changes as shown by an increased length of postsynaptic density, accompanied by an increased expression of plasticity-related proteins such as cAMP-responsive element binding protein phosphorylated at Ser133, calcium-calmodulin-dependent kinase II phosphorylated at Thr286, and brain-derived neurotrophic factor, suggesting a role for Aβ in synaptic tagging. These changes resulted in the conversion of early into late long-term potentiation through the nitric oxide/cGMP/protein kinase G intracellular cascade consistent with a cGMP-dependent switch from short- to long-term memory observed after intrahippocampal administration of picomolar amounts of oAβ These effects were present upon extracellular but not intracellular application of the peptide and involved α7 nicotinic acetylcholine receptors. These observations clarified the physiological role of oAβ in synaptic function and memory formation providing solid fundamentals for investigating the pathological effects of high Aβ levels in the AD brains. High levels of oligomeric amyloid-β (oAβ) induce synaptic dysfunction leading to memory impairment in Alzheimer's disease (AD). However, at picomolar concentrations, the peptide is needed to ensure long-term potentiation (LTP) and memory. Here, we show that extracellular 200 pm oAβ concentrations increase neurotransmitter release, number of docked vesicles, postsynaptic density length, and expression of plasticity-related proteins leading to the conversion of early LTP into late LTP and of short-term memory into long-term memory. These effects require α7 nicotinic acetylcholine receptors and are mediated through the nitric oxide/cGMP/protein kinase G pathway. The knowledge of Aβ function in the healthy brain might be useful to understand the causes leading to its increase and detrimental effect in AD.
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http://dx.doi.org/10.1523/JNEUROSCI.0163-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650983PMC
July 2019

Synaptic vesicle protein 2: A multi-faceted regulator of secretion.

Semin Cell Dev Biol 2019 11 21;95:130-141. Epub 2019 Mar 21.

Department of Pharmacology, University of Washington, Seattle, WA, United States. Electronic address:

Synaptic Vesicle Protein 2 (SV2) comprises a recently evolved family of proteins unique to secretory vesicles that undergo calcium-regulated exocytosis. In this review we consider SV2s' structural features, evolution, and function and discuss its therapeutic potential as the receptors for an expanding class of drugs used to treat epilepsy and cognitive decline.
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http://dx.doi.org/10.1016/j.semcdb.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754320PMC
November 2019

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

Nat Neurosci 2019 04 25;22(4):565-575. Epub 2019 Feb 25.

Department of Pharmacology, University of Washington, Seattle, WA, USA.

Avoidance of innate threats is often in conflict with motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach-avoidance conflict are not well resolved. Here we isolated a population of dopamine D1 receptor (D1R)-expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentially innervate the ventromedial hypothalamus and bed nucleus of the stria terminalis, and these projections have opposing effects on investigation or avoidance of threatening stimuli. These projections are potently modulated through opposite actions of D1R signaling that bias approach behavior. These data demonstrate divergent pathways in the MeApv that can be differentially weighted toward exploration or evasion of threats.
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http://dx.doi.org/10.1038/s41593-019-0337-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446555PMC
April 2019

Two Behavioral Tests Allow a Better Correlation Between Cognitive Function and Expression of Synaptic Proteins.

Front Aging Neurosci 2018 4;10:91. Epub 2018 Apr 4.

Center for Neurobiology of Aging, INRCA, IRCCS, Ancona, Italy.

The molecular substrate of age-associated cognitive decline (AACD) is still elusive. Evidence indicates that AACD is related to synaptic impairment in hippocampus, but different hippocampal regions play different roles, with the dorsal hippocampus (DH) associated to spatial learning, and the ventral hippocampus (VH) crucial for emotionality. If changes in hippocampal function contributes to AACD, this contribution may be reflected in alterations of synaptic protein levels. A commonly used approach to investigate this issue is western blotting. When this technique is applied to the entire hippocampus and the cognitive impairment is evaluated by a single task, changes in expression of a protein might undergo a "dilution effect", as they may occur only in a given hippocampal region. We show that two behavioral tests yield more accurate results than one test in evaluating the function of the whole rat hippocampus by studying the expression of synaptotagmin 1 (SYT1), a vesicular protein whose expression in aged hippocampus is reportedly inconsistent. Analysis of SYT1 levels in the whole hippocampus of rats selected by the Morris water maze (MWM) test only failed to highlight a difference, whereas analysis of SYT1 levels in the whole hippocampus of rats categorized by both the MWM and the step-through passive avoidance (STPA) tests demonstrated a significant increase of SYT1 level in impaired rats. These findings, besides showing that SYT1 increases in impaired aged rats, suggest that using the whole hippocampus in blotting studies may prevent false negative results only if animals are categorized with tests exploring both DH and VH.
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http://dx.doi.org/10.3389/fnagi.2018.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893842PMC
April 2018

Levetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex.

Front Cell Neurosci 2017 11;11:389. Epub 2017 Dec 11.

Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.

Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects.
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http://dx.doi.org/10.3389/fncel.2017.00389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732259PMC
December 2017
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