Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs.

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.

Refractory tonic-myoclonic status epilepticus with catamenial recurrence in epilepsy with myoclonic atonic seizures: A case report.

In epilepsy with myoclonic-atonic seizures (EMA), status epilepticus (SE) may occur during the onset phase, uncommonly in post-puberal patients. We report a post-puberal patient with EMA who presented SE with insidious onset and catamenial recurrence. She had a stormy epilepsy onset at 4 years, with tonic seizures, atypical absences, and myoclonic-atonic seizures, in the absence of SE. After the onset phase, sporadic nocturnal tonic seizures persisted and a mild intellectual disability appeared. At the age of 7, after gonadotropin-releasing hormone analog administration due to central precocious puberty, she presented with SE characterized by recurrent atypical absences, tonic seizures, and awareness impairment, which was successfully treated in 4 days. At 11 years, one week before menstruation, the patient presented with analogous SE that lasted 8 days. One week before the subsequent menstruation, she presented again with SE, initially characterized by atypical absences alternating with phases of awareness and motor impairment related to fast low-voltage EEG activity in the central regions; later, tonic and myoclonic seizures occurring even in the awake state increased, and the "atonic-akinetic status" related to fast EEG activity worsened. After conventional antiepileptic drugs had failed to control the seizures, a progestin was added, with subsequent gradual complete recovery.

Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia.

INTRODUCTION: We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis. METHODS: The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants. RESULTS: TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P < 0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected. DISCUSSION: TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients.

Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations.

Introduction: Recombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation. Methods: In this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1F971L/F971L and Rag1R972Q/R972Q), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter. Results and discussion: Starting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigenspecific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in thesehighly complex patients.

Psychophysiological and Neurophysiological Correlates of Dropping Objects from Hands in Carpal Tunnel Syndrome.

BACKGROUND: Dropping objects from hands (DOH) is a common symptom of carpal tunnel syndrome (CTS). We evaluated the clinical, neurophysiological, and psychophysiological features of 120 CTS patients to elucidate the DOH pathophysiology. Forty-nine healthy controls were included. METHODS: In the patients, the Boston Carpal Tunnel Questionnaire (BCTQ), the Douleur Neuropathique 4 questions (DN4), and a numeric rating scale for pain (NRS) were evaluated. In patients and controls, we evaluated bilateral median and ulnar motor and sensory nerve conduction studies, cutaneous silent period and cutaneomuscular reflexes (CMR) of the abductor pollicis brevis, cold-detection threshold (CDT) and heat-pain detection threshold (HPT) at the index, little finger, and dorsum of the hand, and vibratory detection threshold at the index and little finger by quantitative sensory testing. RESULTS: CTS with DOH had higher BCTQ, DN4 and NRS, lower median sensory action potential, longer CMR duration, lower CDT and higher HPT at all tested sites than controls and CTS without DOH. Predictive features for DOH were abnormal CDT and HPT at the right index and dorsum (OR: 3.88, p: 0.03) or at the little finger (OR: 3.27, p: 0.04) and a DN4 higher than 4 (OR: 2.16, p < 0.0001). CONCLUSIONS: Thermal hypoesthesia in median and extra-median innervated territories and neuropathic pain are predictive of DOH in CTS.

The role of early attachment experiences in modulating defensive peripersonal space.

Selecting appropriate defensive behaviours for threats approaching the space surrounding the body (peripersonal space, PPS) is crucial for survival. The extent of defensive PPS is measured by recording the hand-blink reflex (HBR), a subcortical defensive response. Higher-order cortical areas involved in PPS representation exert top-down modulation on brainstem circuits subserving HBR. However, it is not yet known whether pre-existing models of social relationships (internal working models, IWM) originating from early attachment experiences influence defensive responses. We hypothesized that organized IWM ensure adequate top-down regulation of brainstem activity mediating HBR, whereas disorganized IWM are associated with altered response patterns. To investigate attachment-dependent modulation on defensive responses, we used the Adult Attachment Interview to determine IWM and recorded HBR in two sessions (with or without the neurobehavioral attachment system activated). As expected, the HBR magnitude in individuals with organized IWM was modulated by the threat proximity to the face, regardless of the session. In contrast, for individuals with disorganized IWM, attachment system activation enhances HBR regardless of the threat position, suggesting that triggering emotional attachment experiences magnifies the threatening valence of external stimuli. Our results indicate that the attachment system exerts a strong modulation on defensive responses and the magnitude of PPS.

Imaging and micro-invasive analyses of black stains on the passepartout of Codex Atlanticus Folio 843 by Leonardo da Vinci.

This paper accounts for the diagnostic campaign aimed at understanding the phenomenon of black stains appeared on the passepartout close to the margins of Folio 843 of Leonardo da Vinci's Codex Atlanticus. Previous studies excluded microbiological deterioration processes. The study is based on a multi-analytical approach, including non-invasive imaging measurements of the folio, micro-imaging and synchrotron spectroscopy investigations of passepartout fragments at different magnifications and spectral ranges. Photoluminescence hyperspectral and lifetime imaging highlighted that black stains are not composed of fluorescent materials. µATR-FTIR imaging of fragments from the passepartout revealed the presence of a mixture of starch and PVAc glues localized only in the stained areas close to the margin of the folio. FE-SEM observations showed that the dark stains are localized inside cavities formed among cellulose fibers, where an accumulation of inorganic roundish particles (∅100-200 nm in diameter size), composed of Hg and S, was detected. Finally, by employing synchrotron µXRF, µXANES and HR-XRD analyses it was possible to identify these particles as metacinnabar (ß-HgS). Further research is needed to assess the chemical process leading to the metacinnabar formation in the controlled conservation condition of Leonardo's Codex.

Adaptive behaviour in adolescents and adults with Dravet syndrome.

AIM: To explore the feasibility of using an adaptive behaviour profile (ABP) assessment generated from a well-known measure-the Vineland Adaptive Behavior Scales, Second Edition (VABS-II)-as an instrument for outcome measures in adolescents and adults with Dravet syndrome. METHOD: We administered the VABS-II to 35 adolescents and adults with Dravet syndrome (15 males; mean age 24 years, SD 8 years, range: 12-46 years) and collected epilepsy history and neurological features at the time of assessment. We conducted a cross-sectional analysis of VABS-II raw scores and performed cluster analysis to identify different subgroups. We then explored possible relationships between clinical and epilepsy features, ABPs, and age. RESULTS: Most participants obtained the minimum standard scores in the various VABS-II subdomains, while the raw score analysis outlined interindividual and intraindividual differences among skills. We found two subpopulations: one with a 'lower' ABP and one with a 'higher' ABP, corresponding respectively to individuals in whom myoclonic seizures or generalized spike-and-wave activity were present ('complete phenotype') or absent ('incomplete phenotype') on electroencephalography. INTERPRETATION: This study further delineates the natural history of Dravet syndrome. The assessment of an ABP through the VABS-II raw score analysis provides a means by which to illustrate profiles of adaptive behaviour in adolescents and adults with Dravet syndrome but shows limitations related to poor sensitivity in measuring fine clinical details. There is a need for new and more specific tools to monitor patients with developmental and epileptic encephalopathies. WHAT THIS PAPER ADDS: Most adults with Dravet syndrome obtained the minimum standard scores in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) subdomains. The VABS-II raw score analysis showed interindividual and intraindividual variability. Individuals with myoclonic seizures and/or generalized spike-and-wave activity on electroencephalography showed a worse adaptive behaviour profile.

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease.

BACKGROUND: In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn. METHODS: NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn. RESULTS: In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD. CONCLUSION: In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.

Non-convulsive febrile status epilepticus mimicking a postictal state after a febrile seizure: an ictal electroclinical and evolutive study.

Febrile status epilepticus evolves from a febrile seizure (FS) in 5% of cases. Its prompt recognition is challenging, especially when motor manifestations are absent or subtle. We describe the ictal electroclinical features of non-convulsive febrile status epilepticus (NCFSE) following an apparently concluded FS, initially misinterpreted as postictal obtundation and in some way mimicking the described "non-epileptic twilight state". We present an electroclinical study of 18 children, collected in our unit, who presented with NCFSE after an apparently resolved FS, longitudinally followed for one year to seven years and nine months (mean: four years and three months). The age at first NCFSE ranged between one year and two months and five years and eight months (mean: two years and six months). Patients were examined after spontaneous or rectal diazepam-induced resolution of a FS, while showing persisting impairment of awareness. A lack of responsiveness to painful stimulation, abnormal posturing and aphasia were present in all cases, variably associated with perioral cyanosis, hypersalivation, automatisms, gaze deviation and other lateralizing signs; eyes were open. The EEG recording started 20 to 140 minutes after the apparent resolution of the FS and was invariably characterized by delta or theta-delta pseudorhythmic activity, mainly involving the fronto-temporal regions, with hemispheric predominance in two thirds of the cases. The electroclinical condition, lasting 25 to 210 minutes, quickly recovered after intravenous diazepam. Follow-up revealed normal neurodevelopment and EEG in almost all patients (learning disability emerged in three). In five subjects, NCSE relapsed (twice in two). None presented afebrile seizures. Our series highlights the electroclinical features of focal NCFSE. Distinctive elements are a lack of reactivity, cyanosis, lateralizing clinical and EEG signs, and resolution clearly tied to intravenous benzodiazepine administration.

Expanding the genetic and phenotypic spectrum of CHD2-related disease: From early neurodevelopmental disorders to adult-onset epilepsy.

CHD2 encodes the chromodomain helicase DNA-binding protein 2, an ATP-dependent enzyme that acts as a chromatin remodeler. CHD2 pathogenic variants have been associated with various early onset phenotypes including developmental and epileptic encephalopathy, self-limiting or pharmacoresponsive epilepsies and neurodevelopmental disorders without epilepsy. We reviewed 84 previously reported patients carrying 76 different CHD2 pathogenic or likely pathogenic variants and describe 18 unreported patients carrying 12 novel pathogenic or likely pathogenic variants, two recurrent likely pathogenic variants (in two patients each), three previously reported pathogenic variants, one gross deletion. We also describe a novel phenotype of adult-onset pharmacoresistant epilepsy, associated with a novel CHD2 missense likely pathogenic variant, located in an interdomain region. A combined review of previously published and our own observations indicates that although most patients (72.5%) carry truncating CHD2 pathogenic variants, CHD2-related phenotypes encompass a wide spectrum of conditions with developmental delay/intellectual disability (ID), including prominent language impairment, attention deficit hyperactivity disorder and autistic spectrum disorder. Epilepsy is present in 92% of patients with a median age at seizure onset of 2 years and 6 months. Generalized epilepsy types are prevalent and account for 75.5% of all epilepsies, with photosensitivity being a common feature and adult-onset nonsyndromic epilepsy a rare presentation. No clear genotype-phenotype correlation has emerged.

Epilepsy features in ARID1B-related Coffin-Siris syndrome.

Coffin-Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1B gene in over half of the cases. While the clinical characteristics of the syndrome have been increasingly described, a detailed evaluation of the epileptic phenotype in patients with ARID1B alterations and CSS has not been approached yet. We report seven patients with ARID1B-related CSS, focusing on epilepsy and its electroclinical features. The evolution of epilepsy and EEG findings of children with CSS are described and compared with patients previously reported in the literature. The patients described here reveal common features, consistent with those of patients previously described in the literature. The epilepsy phenotype of CSS due to ARID1B pathogenic variants may be described as focal epilepsy with seizures, variable in frequency, arising from motor areas, with onset in the first years of life and susceptibility to fever, and interictal perisylvian (centrotemporal) epileptiform abnormalities that are enhanced during sleep with possible evolution to an EEG pattern of continuous spike and wave during sleep (without documented developmental regression). Additional information emerging from other patients is needed to confirm this definition.

PBX1-directed stem cell transcriptional program drives tumor progression in myeloproliferative neoplasm.

PBX1 regulates the balance between self-renewal and differentiation of hematopoietic stem cells and maintains proto-oncogenic transcriptional pathways in early progenitors. Its increased expression was found in myeloproliferative neoplasm (MPN) patients bearing the JAK2V617F mutation. To investigate if PBX1 contributes to MPN, and to explore its potential as therapeutic target, we generated the JP mouse strain, in which the human JAK2 mutation is induced in the absence of PBX1. Typical MPN features, such as thrombocythemia and granulocytosis, did not develop without PBX1, while erythrocytosis, initially displayed by JP mice, gradually resolved over time; splenic myeloid metaplasia and in vitro cytokine independent growth were absent upon PBX1 inactivation. The aberrant transcriptome in stem/progenitor cells from the MPN model was reverted by the absence of PBX1, demonstrating that PBX1 controls part of the molecular pathways deregulated by the JAK2V617F mutation. Modulation of the PBX1-driven transcriptional program might represent a novel therapeutic approach.

Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency.

Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII-/- mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII-/- mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency.

Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased ß-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.

eStroop: Implementation, Standardization, and Systematic Comparison of a New Voice-Key Version of the Traditional Stroop Task.

The Stroop effect is a well-documented phenomenon, demonstrating both interference and facilitation effects. Many versions of the Stroop task were created, according to the purposes of its applications, varying in numerous aspects. While many versions are developed to investigate the mechanisms of the effect itself, the Stroop effect is also considered a general measure of attention, inhibitory control, and executive functions. In this paper, we implement "eStroop": a new digital version based on verbal responses, measuring the main processes involved in the traditional effect. eStroop features four categories of stimuli in four different colors: (1) geometrical shapes, (2) neutral words, (3) congruent words, and (4) incongruent words. The results of the administration to 307 University students confirm the Stroop effect and offer baseline data for future research and clinical testing. Direct comparisons with other recent versions of the task are discussed, offering insights into differences and similarities between different task variables.

CDKL5 deficiency disorder in males: Five new variants and review of the literature.

The X-linked Cyclin-Dependent Kinase-Like 5 (CDKL5) gene encodes a serine-threonine kinase highly expressed in the developing brain. Loss of function of CDKL5 is pointed out to underlie the CDKL5 Deficiency Disorder (CDD), an X-linked dominant disease characterized by early-onset epileptic encephalopathy and developmental delay, usually affecting females more than males. To the best to our knowledge, only 45 males with CDD have been reported so far. Type and position of CDKL5 variants with different impact on the protein are reported to influence the clinical presentation. X-chromosome inactivation occurring in females and post-zygotic mosaicism in males are also believed to contribute to this variability. Based on these issues, genotype-phenotype correlations are still challenging. Here, we describe clinical features of five additional affected males with unreported CDKL5 variants, expanding the molecular spectrum of the disorder. We also reviewed the clinical profile of the previously reported 45 males with molecularly confirmed CDD. Severe developmental delay, cortical visual impairment, and early-onset refractory epilepsy characterize the CDD picture in males. By assessing the molecular spectrum, we confirm that germ-line truncating CDKL5 variants, equally distributed across the coding sequence, are the most recurrent mutations in CDD, and cause the worsen phenotype. While recurrence and relevance of missense substitutions within C-terminal remain still debated, disease-causing missense changes affecting the N-terminal catalytic domain correlate to a severe clinical phenotype. Finally, our data provide evidence that post-zygotic CDKL5 mosaicism may result in milder phenotypes and, at least in a subset of subjects, in variable response to antiepileptic treatments.

Remote Teamwork Management of NORSE During the COVID-19 Lockdown.

New-onset refractory status epilepticus (NORSE) is rare condition, and sharing knowledge is vital in its management, based on strict collaboration between multiple specialists, continuous EEG (c-EEG) monitoring, and prompt therapy modification. The coronavirus disease 2019 (COVID-19) pandemic challenged many of these established practices because of "social distancing" measures, making it necessary to work around physical restrictions. We report a case of a 10-year-old with NORSE admitted in a pediatric intensive-care unit and monitored with c-EEG and amplitude-integrated EEG. The monitoring interface was livestreamed using videoconference web-based platforms allowing remote viewing. Multiple daily web meetings took place between team members, where real-time therapy response was evaluated and confronted with medium-term trends in the epileptic activity, dictating further treatment and diagnostic steps. In addition to the known use of telemedicine in chronic conditions, we report how its use can be exploited to treat urgent conditions such as NORSE. By taking advantage of new tools and virtual environments, we were able to share treatment and diagnostic decisions and guarantee real-time therapy adjustments and a coherent course in treatment despite restrictions necessary for the COVID-19 pandemic. The constant specialist monitoring and the coherent and on-time communication of the patient's condition relieved the family stress, usually complained in these situations.