المؤلفون: Cinzia Costa, Elena Nardi Cesarini, Paolo Eusebi, David Franchini, Paola Casucci, Marcello De Giorgi, Carmen Calvello, Michele Romoli, Lucilla Parnetti, Paolo Calabresi

المصدر: Frontiers in Neurology
Frontiers in Neurology, Vol 12 (2022)

مصطلحات موضوعية: administrative databases, Settore MED/26 - NEUROLOGIA, Neurology, incidence, epilepsy, Neurology. Diseases of the nervous system, Neurology (clinical), respiratory system, RC346-429, antiseizure medications, stroke, Original Research

الوصف: Introduction: Post-stroke epilepsy (PSE) requires long-term treatment with antiseizure medications (ASMs). However, epidemiology of PSE and long-term compliance with ASM in this population are still unclear. Here we report, through population-level healthcare administrative data, incidence, risk factors, ASM choice, and ASM switch over long-term follow-up.Materials and Methods: This is a population-based retrospective study using Umbria healthcare administrative database. Population consisted of all patients with acute stroke, either ischaemic or hemorrhagic, between 2013 and 2018. ICD-9-CM codes were implemented to identify people with stroke, while PSE was adjudicated according to previously validated algorithm, such as EEG and ≥1 ASM 7 days after stroke.Results: Overall, among 11,093 incident cases of acute stroke (75.9% ischemic), 275 subjects presented PSE, for a cumulative incidence of 2.5%. Patients with PSE were younger (64 vs. 76 years), more frequently presented with hemorrhagic stroke, and had longer hospital stay (15.5 vs. 11.2 days) compared with patients without PSE. Multivariable Cox proportional hazards models confirmed that PSE associated with hemorrhagic stroke, younger age, and longer duration of hospital stay. Levetiracetam was the most prescribed ASM (55.3%), followed by valproate and oxcarbazepine. Almost 30% of patients prescribed with these ASMs switched treatment during follow-up, mostly toward non-enzyme-inducing ASMs. About 12% of patients was prescribed ASM polytherapy over follow-up.Conclusions: Post-stroke epilepsy is associated with hemorrhagic stroke, younger age, and longer hospital stay. First ASM is switched every one in three patients, suggesting the need for treatment tailoring in line with secondary prevention.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::472adc957199f818cb925a6c891cf7abTest
https://doi.org/10.3389/fneur.2021.800524Test

المؤلفون: Giulia Campostrini, Jacopo C. DiFrancesco, Barbara Castellotti, Raffaella Milanesi, Tomaso Gnecchi-Ruscone, Mattia Bonzanni, Annalisa Bucchi, Mirko Baruscotti, Carlo Ferrarese, Silvana Franceschetti, Laura Canafoglia, Francesca Ragona, Elena Freri, Angelo Labate, Antonio Gambardella, Cinzia Costa, Cinzia Gellera, Tiziana Granata, Andrea Barbuti, Dario DiFrancesco

المساهمون: Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D

المصدر: Frontiers in Molecular Neuroscience, Vol 11 (2018)

مصطلحات موضوعية: 0301 basic medicine, Bradycardia, Gene isoform, Mutant, medicine.disease_cause, Epilepsy, HCN4, Ion channels, Myoclonic epilepsy of infancy, Neuronal excitability, Molecular Biology, Cellular and Molecular Neuroscience, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Loss function, Mutation, business.industry, medicine.disease, 030104 developmental biology, Etiology, Myoclonic epilepsy, medicine.symptom, Ion channel, business, Neuroscience, 030217 neurology & neurosurgery

الوصف: HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::595be110fcea99e6a2163f6032d312deTest
https://doi.org/10.3389/fnmol.2018.00269Test

المؤلفون: Valentina Durante, Carmela Giampà, Ana Quiroga-Varela, Michela Di Mauro, Antonio de Iure, Vito Enrico Pettorossi, Silvarosa Grassi, Michela Tantucci, Massimiliano Di Filippo, Alessandro Tozzi, Paolo Calabresi, Cinzia Costa, Petra Mazzocchetti

المصدر: Frontiers in Cellular Neuroscience

مصطلحات موضوعية: Neuroactive steroid, Settore BIO/09 - FISIOLOGIA, striatum, medium spiny neurons, D1 receptor, P450-aromatase, Striatum, Biology, Medium spiny neuron, Cellular and Molecular Neuroscience, Dopamine, medicine, estrogen receptors, synaptic plasticity, long-term potentiation, cholinergic interneurons, Receptor, Original Research, Dopaminergic, Long-term potentiation, estrogen receptors, P450-aromatase, striatum, synaptic plasticity, long-term potentiation, medium spiny neurons, cholinergic interneurons, D1 receptor, nervous system, Synaptic plasticity, Neuroscience, medicine.drug

الوصف: 17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a1d9a759a527c10a2d6e55538fd6b53Test