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1.
J Pineal Res ; 76(1): e12932, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38111174

RESUMO

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns.


Assuntos
Melatonina , Nascimento Prematuro , Feminino , Recém-Nascido , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Melatonina/uso terapêutico , Recém-Nascido Prematuro , Espécies Reativas de Oxigênio , Neuroproteção , Estudos Prospectivos
2.
Am J Med Genet A ; 191(7): 1953-1958, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37067188

RESUMO

PUS7 gene pathogenic variants cause a deficiency in an RNA-independent pseudouridine synthase, which results in a neurodevelopmental phenotype characterized by various degrees of psychomotor delay, acquired microcephaly, aggressive behavior, and intellectual disability. Since 2018, PUS7 deficiency has been described in 15 patients with different pathogenic variants but similar clinical phenotypes. We describe the case of a male infant with a homozygous truncating pathogenic variant in the PUS7 gene (c.329_332delCTGA; p.Thr110Argfs*4) who, in addition to the previously mentioned features, displays self-injurious behavior, sleep disturbances and motor stereotypies.


Assuntos
Deficiência Intelectual , Microcefalia , Comportamento Autodestrutivo , Humanos , Masculino , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Microcefalia/diagnóstico , Microcefalia/genética , Microcefalia/patologia , Fenótipo , Comportamento Autodestrutivo/complicações , Comportamento Autodestrutivo/genética , Sono
3.
Neurol Sci ; 44(1): 45-58, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36114980

RESUMO

OBJECTIVE: Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing-remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability. The identification of signs, symptoms, markers of progression, and strategies to manage MS patients is mandatory to allow early identification of those at higher risk of conversion to SPMS, for prompt intervention to cope with the progression of the disease. METHODS: A panel of Italian experts from Southern Italy have reviewed the current knowledge on MS and its management and identified the crucial tools for SPMS recognition. RESULTS: More effective communication between patients and clinicians should be established, with the support of digital tools. Moreover, the improvement in the clinical use of biomarkers for progression (cellular structures and tissue organization, such as neurofilaments and chitinase 3-like 1, axonal and neurons density) and of instrumental analyses for recognition of whole-brain atrophy, chronic active lesions, spinal cord lesions and atrophy, and the improvement the combination of the Expanded Disability Status Scale and the evaluation of cognitive dysfunction are discussed. CONCLUSION: Given the availability of a pharmacological option, adequate education both for patients, regarding the evolution of the disease and the specific treatment, and for professionals, to allow more effective and sensitive communication and the best use of diagnostic and management tools, could represent a strategy to improve patient management and their quality of life.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Qualidade de Vida , Progressão da Doença , Recidiva Local de Neoplasia , Esclerose Múltipla Crônica Progressiva/diagnóstico , Itália , Atrofia , Atenção à Saúde
4.
Am J Med Genet A ; 185(8): 2526-2531, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008900

RESUMO

Cerebral folate transporter deficiency syndrome, caused by FOLR-1 mutations is characterized by late infantile onset, severe developmental regression, epilepsy, and leukodystrophy. An extremely low concentration of 5-methyltetrahydrofolate in the cerebrospinal fluid provides a crucial clue to its diagnosis and is a treatment target. Oral or intravenous folinic acid (5-formyltetrahydrofolate) administration improves clinical symptoms and brain magnetic resonance imaging (MRI) findings. We describe three siblings carrying a novel homozygous FOLR1 nonsense mutation, that were referred due to intractable epilepsy and progressive neurological decline. Brain MRI showed hypomyelination and cerebellar atrophy. Folinic acid (oral and intravenous) supplementation, initiated after over 15 years illness, has failed to result in any sizeable clinical or neurophysiological improvement. Cerebral folate transport deficiency bears overlapping clinical features with many severe developmental encephalopathies. It is crucial to recognize FOLR1 signs and establish an early clinical and molecular diagnosis in order to provide timely folinic acid treatment and improve outcome.


Assuntos
Receptor 1 de Folato/deficiência , Estudos de Associação Genética , Predisposição Genética para Doença , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/genética , Irmãos , Adolescente , Alelos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Consanguinidade , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Gerenciamento Clínico , Epilepsia/diagnóstico , Epilepsia/genética , Feminino , Receptor 1 de Folato/genética , Ácido Fólico/administração & dosagem , Testes Genéticos , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação , Distrofias Neuroaxonais/terapia , Fenótipo , Síndrome , Resultado do Tratamento
5.
Seizure ; 61: 1-3, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30029089

RESUMO

PURPOSE: Children with Childhood Absence Epilepsy (CAE) may develop generalized tonic-clonic seizure or juvenile myoclonic epilepsy. A possible evolution to Eyelid Myoclonia with Absence Epilepsy (EMA) hasn't been documented yet. We report the electroclinical features of a case series of children with CAE that evolved to EMA after therapy withdrawal. METHOD: Of 108 patients with CAE referred at our Epilepsy Center in the last ten years, 5 satisfied the inclusion criteria: CAE diagnosis, a minimum of 3 years follow-up, a progression to EMA after therapy withdrawal. RESULTS: All the six subjects were females. CAE was characterized by typical absences induced by hyperventilation; intermittent photic stimulation (IPS) was negative. All subjects were treated successfully with valproate. After drug withdrawal, all the six girls presented EMA. EMA was characterized by eyelid myoclonia with or without brief absences related to generalized spike/polyspike-waves discharges induced by IPS and less frequently by eye-closure. CONCLUSIONS: Our study documented another possible evolution of CAE into EMA. These results support the hypothesis that these two epileptic conditions are dynamic processes evolving into one another. CAE and EMA could be considered "system epilepsy" characterized by a high susceptibility to changes in the brain networks during specific life periods such as childhood and puberty.


Assuntos
Epilepsia Tipo Ausência/complicações , Epilepsia Mioclônica Juvenil/etiologia , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Progressão da Doença , Eletroencefalografia , Epilepsia Tipo Ausência/diagnóstico por imagem , Epilepsia Tipo Ausência/tratamento farmacológico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Epilepsia Mioclônica Juvenil/diagnóstico por imagem , Estudos Retrospectivos , Ácido Valproico/uso terapêutico
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