Case Report: Ictal Central Apnea as First and Overlooked Symptom in Temporal Lobe Seizures

Ictal respiratory changes have been mainly described following generalized tonic-clonic seizures and recently considered to be a biomarker to assess the risk of sudden unexplained death in epilepsy (SUDEP). Nonetheless, modification of respiratory pattern can be related also to focal seizures, especially arising from the temporal lobe. Changes in cardiac function such as tachycardia or bradycardia could be often associated. We report a short case series of four patients with temporal lobe epilepsy admitted to our Epilepsy Monitoring Unit (EMU) presenting with an ictal central apnea as the first clinical manifestation of their seizures. None of these patients was aware of the occurrence of respiratory arrest. Age at onset ranged from 15 to 29 years. One patient had seizures with prolonged central apnea accompanied by a significant decrease in oxygen saturation. Neuroimaging in two patients showed alterations of mesial temporal lobe structures, including the amygdala. Recent neurophysiological studies supported the existence of a cortical network involving the limbic system that modulates downstream brainstem respiratory centers. Monitoring for respiratory changes and oxygen saturation in focal seizures is warranted for their potential value in identifying the epileptogenic zone and for a better understanding of ictal respiratory changes that could potentially define a subgroup of patients with high risk of seizure-related autonomic changes

Valorization of a Levulinic Acid Platform through Electrospinning of Polyhydroxyalkanoate-Based Fibrous Membranes for in Vitro Modeling of Biological Barriers

In vitro models of biological barriers provide a reliable tool for investigating the physiopathological processes involved in the development of numerous diseases. Producing sustainable in vitro models obtained from solvents and biopolymers derived from industrial by-products add an important value to this underestimated source of valuable (bio)materials. This works aims at demonstrating the suitability of processing together solvents derived from levulinic acid (LA) (extracted from biomasses) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) (whose production is facilitated by LA) to produce electrospun membranes as proof-of-concept of a sustainable, engineered biological barrier fully derived from LA as the starting feedstock. The electrospinning process is initially optimized by identifying the most suitable conditions for obtaining self-supporting microporous membranes. In particular, LA-derived solvents (γ-valerolactone, 2-methyltetrahydrofuran, methyl ethyl ketone, and methyl and ethyl levulinate), PHBV concentration, and electrospinning process parameters were investigated. Self-standing and hydrophobic PHBV mats with a micropore size in the range of 1–7 μm and an average elastic modulus of 75 MPa are successfully obtained by using methyl ethyl ketone/formic acid as solvent. Preliminary cell experiments demonstrate that the developed fibrous PHBV mats promote the formation of a confluent monolayer of epithelial cells after 48 h and therefore they can potentially be used to mimic biological epithelial barriers

Valorization of not soluble byproducts deriving from green keratin extraction from poultry feathers as filler for biocomposites

The valorization of poultry feathers wastes is very important to reduce the environmental pollution deriving from their disposal. In this frame, we present the production process of completely natural, biodegradable, biocompatible, and eco-friendly composites made by not soluble keratin (NSK) and poly(lactic acid) (PLA). NSK has been obtained as a byproduct of a microwave-assisted keratin extraction from poultry feathers and it has been added to PLA pellets without adding any additional compatibilizers or plasticizers, unlike from the other works reported in the literature until now. The mixture has been used to obtain homogeneous NSK-based PLA filaments by means of hot-melt extrusion technology. The filaments have been subsequently 3D printed to explore applications in the additive manufacturing field. All the samples have unaltered thermal stability, but reduced toughness with respect to neat PLA. Other tested parameters (water adsorption, glass transition, and crystallinity) are dependent on NSK content and fabrication technology. Besides, Fourier Transform Infrared Spectroscopy highlights the differences in the structure of the NSK-based PLA filaments and 3D printed samples

Ictal apnea: A prospective monocentric study in patients with epilepsy

Background and purpose: Ictal respiratory disturbances have increasingly been reported, in both generalized and focal seizures, especially involving the temporal lobe. Recognition of ictal breathing impairment has gained importance for the risk of sudden unexpected death in epilepsy (SUDEP). The aim of this study was to evaluate the incidence of ictal apnea (IA) and related hypoxemia during seizures. Methods: We collected and analyzed electroclinical data from consecutive patients undergoing long-term video-electroencephalographic (video-EEG) monitoring with cardiorespiratory polygraphy. Patients were recruited at the epilepsy monitoring unit of the Civil Hospital of Baggiovara, Modena Academic Hospital, from April 2020 to February 2022. Results: A total of 552 seizures were recorded in 63 patients. IA was observed in 57 of 552 (10.3%) seizures in 16 of 63 (25.4%) patients. Thirteen (81.2%) patients had focal seizures, and 11 of 16 patients showing IA had a diagnosis of temporal lobe epilepsy; two had a diagnosis of frontal lobe epilepsy and three of epileptic encephalopathy. Apnea agnosia was reported in all seizure types. Hypoxemia was observed in 25 of 57 (43.9%) seizures with IA, and the severity of hypoxemia was related to apnea duration. Apnea duration was significantly associated with epilepsy of unknown etiology (magnetic resonance imaging negative) and with older age at epilepsy onset (p < 0.001). Conclusions: Ictal respiratory changes are a frequent clinical phenomenon, more likely to occur in focal epilepsies, although detected even in patients with epileptic encephalopathy. Our findings emphasize the need for respiratory polygraphy during long-term video-EEG monitoring for diagnostic and prognostic purposes, as well as in relation to the potential link of ictal apnea with the SUDEP risk

The role of the amygdala in ictal central apnea: insights from brain MRI morphometry

Objective: Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy.Methods: We prospectively recruited focal epilepsy patients with recorded seizures during a video-EEG long-term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high-resolution T1-weighted images. Post-processing analyses included a whole-brain VBM analysis and segmentation algorithms performed with FreeSurfer.Results: Forty-six patients were recruited (aged 15-60 years): 16 ICA and 30 noICA. The whole-brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub-segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034). Interpretation: Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA

One-pot process: Microwave-assisted keratin extraction and direct electrospinning to obtain keratin-based bioplastic

Poultry feathers are among the most abundant and polluting keratin-rich waste bio-masses. In this work, we developed a one-pot microwave-assisted process for eco-friendly keratin extraction from poultry feathers followed by a direct electrospinning (ES) of the raw extract, without further purification, to obtain keratin-based bioplastics. This microwave-assisted keratin extraction (MAE) was conducted in acetic acid 70% v/v. The effects of extraction time, solvent/feathers ratio, and heating mode (MAE vs conventional heating) on the extraction yield were investigated. The highest keratin yield (26 ± 1% w/w with respect to initial feathers) was obtained after 5 h of MAE. Waste-derived keratin were blended with gelatin to fabricate keratin-based biodegradable and bio-compatible bioplastics via ES, using 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) as a cross-linking agent. A full characterization of their thermal, mechanical, and barrier properties was performed by differential scanning calorimetry, thermogravimetric analysis, uniaxial tensile tests, and water permeability measurements. Their morphology and protein structure were investigated using scanning electron microscopy and attenuated total reflection-infrared spectroscopy. All these characterizations highlighted that the properties of the keratin-based bioplastics can be modulated by changing keratin and GPTMS concentrations. These bioplastics could be applied in areas such as bio-packaging and filtration/purification membranes

GRUND 2008 nella sub area geografica 16 (GSA 16, Stretto di Sicilia): relazione finale

Il progetto Grund, finanziato a partire dal 1985 dapprima dalla D.G. Pesca e Acquacolura del Ministero per le politiche agricole, alimentari e forestali (MIPAAF) con i fondi della legge 41, in seguito dal MIPAAF e dalla DG IV della Commissione Europea, ha l’obiettivo generale di valutare la distribuzione, l’abbondanza e la composizione per taglia delle specie oggetto di pesca presenti nei mari Italiani. L’Istituto di ricerche sulle Risorse Marine e l’Ambiente, Sezione di Mazara del Vallo di IAMC-CNR, effettua campagne di ricerca in mare nella GSA 16 (FAO, 2001) dello Stretto di Sicilia, tramite rete a strascico (trawl survey), sin dalla primavera del 1985, con l’obiettivo generale di studiare l’abbondanza ed i cicli vitali delle risorse demersali e di stimarne lo stato di sfruttamento

Inhibitory 2B4 contributes to NK cell education and immunological derangements in XLP1 patients

X-linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in SH2D1A encoding Signaling Lymphocyte Activation Molecule (SLAM)-associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV-infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of killer Ig-like receptor (KIR)/KIR-L genotype and phenotypic repertoire of self-HLA class I specific inhibitory NK receptors (self-iNKRs). We also analyzed NK-cell cytotoxicity against CD48+ or CD48− KIR-ligand matched or autologous hematopoietic cells in XLP1 patients and healthy controls. XLP1 NK cells may show a defective phenotypic repertoire with substantial proportion of cells lacking self-iNKR. These NK cells are cytotoxic and the inhibitory 2B4/CD48 pathway plays a major role to prevent killing of CD48+ EBV-transformed B cells and M1 macrophages. Importantly, self-iNKR defective NK cells kill CD48− targets, such as mature DCs. Self-iNKR− NK cells in XLP1 patients are functional even in resting conditions, suggesting a role of the inhibitory 2B4/CD48 pathway in the education process during NK-cell maturation. Killing of autologous mature DC by self-iNKR defective XLP1 NK cells may impair adaptive responses, further exacerbating the patients’ immune defect

Clinical variability at the mild end of BRAT1-related spectrum: Evidence from two families with genotype–phenotype discordance

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal to neurodevelopmental disorder, and cerebellar atrophy with or without seizures, without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at the BRAT1 locus. Two siblings displayed nonprogressive congenital ataxia and shrunken cerebellum on magnetic resonance imaging. A third unrelated patient showed normal neurodevelopment, adolescence-onset seizures, and ataxia, shrunken cerebellum, and ultrastructural abnormalities on skin biopsy, representing the mildest form of NEDCAS hitherto described. Exome sequencing identified the c.638dup and the novel c.1395G>A BRAT1 variants, the latter causing exon 10 skippings. The p53-MCL test revealed normal ATM kinase activity. Our findings broaden the allelic and clinical spectrum of BRAT1-related disease, which should be suspected in presence of nonprogressive cerebellar signs, even without a neurodevelopmental disorder