Status epilepticus dynamics predicts latency to spontaneous seizures in the kainic acid model

(TLE), a common neurologic disorder characterized by spontaneous recurrent seizures (SRSs). However, the relationship between SE and TLE is still incompletely characterized. For this reason, in a model of TLE we evaluated the lesion extent and the onset of SRSs to determine if they were influenced by the SE dynamics. Methods: Sixty-two adult male Sprague-Dawley rats were implanted for video-electrocorticographic (v-ECoG) monitoring and intraperitoneally treated with saline or kainic acid (KA, 15 mg/kg) at 8 weeks of age. v-ECoG recordings were obtained during SE, in the following 9 weeks, and assessed by amplitude or power band spectrum. Rats were euthanized 3 or 64 days after SE to evaluate the lesion. Results: SE lasted about 10 h during which the mean duration of convulsive seizures (CSs) increased from 39 s, at 30 min, to 603 s at 4 h. The gamma power peaked 30 min after the SE onset and its peak was correlated (r²=0.13, p=0.042) with the overall SE duration. Subsequently, the gamma power was reduced under the baseline until the end of SE. The theta power increased at approximately 150% of basal levels 3 h after KA injection, but it went back to basal levels with the full development of CSs. Interestingly, the timing of the first SRS in chronic epilepsy was correlated with the latency to develop the first CS with loss of posture during SE (r²=0.60, p<0.001). Additionally, the overall duration of CSs observed during SE was related to the number of damaged brain regions (r²=0.60, p=0.005), but it did not influence the timing of the first SRS in chronic epilepsy. Conclusion: Overall, our results show that the onset of chronic epilepsy is modulated by SE dynamics, whereas brain damage is related to prolonged convulsions in SE

Selenoprotein P Concentrations in the Cerebrospinal Fluid and Serum of Individuals Affected by Amyotrophic Lateral Sclerosis, Mild Cognitive Impairment and Alzheimer’s Dementia

Selenoprotein P, a selenium-transporter protein, has been hypothesized to play a role in the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's dementia (AD). However, data in humans are scarce and largely confined to autoptic samples. In this case-control study, we determined selenoprotein P concentrations in both the cerebrospinal fluid (CSF) and the serum of 50 individuals diagnosed with ALS, 30 with AD, 54 with mild cognitive impairment (MCI) and of 30 controls, using sandwich enzyme-linked immunosorbent assay (ELISA) methods. We found a positive and generally linear association between CSF and serum selenoprotein P concentrations in all groups. CSF selenoprotein P and biomarkers of neurodegeneration were positively associated in AD, while for MCI, we found an inverted-U-shaped relation. CSF selenoprotein P concentrations were higher in AD and MCI than in ALS and controls, while in serum, the highest concentrations were found in MCI and ALS. Logistic and cubic spline regression analyses showed an inverse association between CSF selenoprotein P levels and ALS risk, and a positive association for AD risk, while an inverted-U-shaped relation with MCI risk emerged. Conversely, serum selenoprotein P concentrations were positively associated with risk of all conditions but only in their lower range. Overall, these findings indicate some abnormalities of selenoprotein P concentrations in both the central nervous system and blood associated with ALS and neurocognitive disorders, though in different directions. These alterations may reflect either phenomena of etiologic relevance or disease-induced alterations of nutritional and metabolic status

Intervenciones comunitarias en la educación formal: apuntes de una aproximación a los actores y sus representaciones en contextos de vulnerabilidad social

Este libro presenta una investigación que analiza las representaciones que tienen los diferentes actores sociales respecto de las intervenciones comunitarias que se realizan en instituciones públicas de educación formal en contextos de vulnerabilidad social. El trabajo busca dar cuenta de cuáles son los actores de la comunidad que realizan intervenciones en las instituciones educativas, a qué dimensión de la institución dirigen sus acciones y cuál es la complejidad de las relaciones actor-institución.Agencia Nacional de Investigación e Innovació

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Intervenciones comunitarias en la educación formal: apuntes de una aproximación a los actores y sus representaciones en contextos de vulnerabilidad social

Este libro presenta una investigación que analiza las representaciones que tienen los diferentes actores sociales respecto de las intervenciones comunitarias que se realizan en instituciones públicas de educación formal en contextos de vulnerabilidad social. El trabajo busca dar cuenta de cuáles son los actores de la comunidad que realizan intervenciones en las instituciones educativas, a qué dimensión de la institución dirigen sus acciones y cuál es la complejidad de las relaciones actor-institución.Agencia Nacional de Investigación e Innovació

Prevention of Flare Recurrences in Childhood-Refractory Chronic Uveitis: An Open-LabelComparative Study of Adalimumab Versus Infliximab

Objective. To compare the efficacy and safety of adalimumab versus infliximab in an open-label prospective, compar- ative, multicenter cohort study of childhood noninfectious chronic uveitis. Methods. Thirty-three patients (22 females, 11 males, median age 9.17 years) with refractory, vision-threatening, noninfectious active uveitis were enrolled, and received for at least 1 year infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 6\u20138 weeks) or adalimumab (24 mg/m2 every 2 weeks). The primary outcome was to assess, once remission was achieved, the time of a first relapse. Time to remission, time to steroid discontinuation, and the number of relapses were also considered. Results. Sixteen children (12 with juvenile idiopathic arthritis [JIA], 3 with idiopathic uveitis, and 1 with Behcet\u2019sdisease) were recruited in the adalimumab cohort and 17 children (10 with JIA, 5 with idiopathic uveitis, 1 with early-onset sarcoidosis, and 1 with Behcet\u2019s disease) were recruited in the infliximab group. Cox regression analysis did not show statistically significant differences between the two groups with regard to time to achieve remission and time to steroid discontinuation, whereas a higher probability of uveitis remission on adalimumab during the time of treatment was shown (Mantel-Cox 2 6.83,P < 0.001). At 40 months of followup, 9 (60%) of 15 children receiving adalimumab compared to 3 (18.8%) of 16 children receiving infliximab were still in remission on therapy ( P<0.02). Conclusion. Even if limited to a relatively small group, our study suggests that over 3 years of treatment, adalimumab is more efficacious than infliximab in maintaining remission of chronic childhood uveitis

Data_Sheet_1_Case report: p.Glu134del SOD1 mutation in two apparently unrelated ALS patients with mirrored phenotype.docx

With upcoming personalized approaches based on genetics, it is important to report new mutations in amyotrophic lateral sclerosis (ALS) genes in order to understand their pathogenicity and possible patient responses to specific therapies. SOD1 mutations are the second most frequent genetic cause of ALS in European populations. Here, we describe two seemingly unrelated Italian patients with ALS carrying the same SOD1 heterozygous c.400_402 deletion (p.Glu134del). Both patients had spinal onset in their lower limbs, progressive muscular weakness with respiratory involvement, and sparing bulbar function. In addition to the clinical picture, we discuss the possible pathogenic role of this unfamiliar SOD1 mutation.</p

A Comprehensive Review of COVID-19-Related Olfactory Deficiency: Unraveling Associations with Neurocognitive Disorders and Magnetic Resonance Imaging Findings

Olfactory dysfunction (OD) is one of the most common symptoms in COVID-19 patients and can impact patients’ lives significantly. The aim of this review was to investigate the multifaceted impact of COVID-19 on the olfactory system and to provide an overview of magnetic resonance (MRI) findings and neurocognitive disorders in patients with COVID-19-related OD. Extensive searches were conducted across PubMed, Scopus, and Google Scholar until 5 December 2023. The included articles were 12 observational studies and 1 case report that assess structural changes in olfactory structures, highlighted through MRI, and 10 studies correlating the loss of smell with neurocognitive disorders or mood disorders in COVID-19 patients. MRI findings consistently indicate volumetric abnormalities, altered signal intensity of olfactory bulbs (OBs), and anomalies in the olfactory cortex among COVID-19 patients with persistent OD. The correlation between OD and neurocognitive deficits reveals associations with cognitive impairment, memory deficits, and persistent depressive symptoms. Treatment approaches, including olfactory training and pharmacological interventions, are discussed, emphasizing the need for sustained therapeutic interventions. This review points out several limitations in the current literature while exploring the intricate effects of COVID-19 on OD and its connection to cognitive deficits and mood disorders. The lack of objective olfactory measurements in some studies and potential validity issues in self-reports emphasize the need for cautious interpretation. Our research highlights the critical need for extensive studies with larger samples, proper controls, and objective measurements to deepen our understanding of COVID-19’s long-term effects on neurological and olfactory dysfunctions

Factors predicting disease progression in C9ORF72 ALS patients

To unveil clinical features, comorbidities, disease progression and prognostic factors in a population-based cohort of ALS patients carrying C9ORF72 expansion (C9 + ALS)