Anomalous spin precession systematic effects in the search for a muon EDM using the frozen-spin technique.

At the Paul Scherrer Institut (PSI), we are developing a high-precision apparatus with the aim of searching for the muon electric dipole moment (EDM) with unprecedented sensitivity. The underpinning principle of this experiment is the frozen-spin technique, a method that suppresses the spin precession due to the anomalous magnetic moment, thereby enhancing the signal-to-noise ratio for EDM signals. This increased sensitivity enables measurements that would be difficult to achieve with conventional g-2 muon storage rings. Given the availability of the 125MeV/c muon beam at PSI, the anticipated statistical sensitivity for the EDM after a year of data collection is 6×10-23e·cm. To achieve this goal, it is imperative to do a detailed analysis of any potential spurious effects that could mimic EDM signals. In this study, we present a quantitative methodology to evaluate the systematic effects that might arise in the context of the frozen-spin technique utilised within a compact storage ring. Our approach involves the analytical derivation of equations governing the motion of the muon spin in the electromagnetic (EM) fields intrinsic to the experimental setup, validated through numerical simulations. We also illustrate a method to calculate the cumulative geometric (Berry's) phase. This work complements ongoing experimental efforts to detect a muon EDM at PSI and contributes to a broader understanding of spin-precession systematic effects.

Simultaneous seroprevalence of Toxoplasma gondii and rubella virus infections in pregnant women in Dakar (Senegal).

Context: Toxoplasma gondii and rubella virus are microorganisms that can cause intrauterine infections and congenital anomalies in the fetus. Data regarding the simultaneous seroprevalence of these infections are not available in Senegal. Aims: This study aimed to determine for the first time the simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Dakar. Materials and Methods: In this retrospective study, anti-Toxoplasma and anti-rubella antibodies were analyzed in the serum samples obtained from pregnant women receiving prenatal care at Military Hospital of Ouakam between 2016 and 2021 using a chemiluminescent microparticle immunoassay for the quantitative determination of immunoglobulin G (IgG) and IgM antibodies to Toxoplasma gondii and rubella in human serum. Results: Overall, data from 2589 women were analyzed. The median age was 29 years (interquartile range: 23.14-34.86). Serum IgG and IgM were positive for T. gondii with 35.84% and 1.66%, respectively. Rubella seroprevalence was 87.14% and 0.35%, respectively, for IgG and IgM. Seroprevalence of toxoplasmosis increases significantly with age and study period. For rubella infection, the highest seroprevalence rates were noted in the youngest age group and at the end of the study period. Conclusions: Data from this first-time study regarding simultaneous seroprevalence of toxoplasmosis and rubella among pregnant women in Senegal indicate a continuing high risk of congenital toxoplasmosis and congenital rubella syndrome in Dakar. Further studies are needed to fully assess the efficacy of rubella vaccination in women of childbearing age.

Assessing the quality of data for drivers of disease emergence.

Drivers are factors that have the potential to directly or indirectly influence the likelihood of infectious diseases emerging or re-emerging. It is likely that an emerging infectious disease (EID) rarely occurs as the result of only one driver; rather, a network of sub-drivers (factors that can influence a driver) are likely to provide conditions that allow a pathogen to (re-)emerge and become established. Data on sub-drivers have therefore been used by modellers to identify hotspots where EIDs may next occur, or to estimate which sub-drivers have the greatest influence on the likelihood of their occurrence. To minimise error and bias when modelling how sub-drivers interact, and thus aid in predicting the likelihood of infectious disease emergence, researchers need good-quality data to describe these sub-drivers. This study assesses the quality of the available data on sub-drivers of West Nile virus against various criteria as a case study. The data were found to be of varying quality with regard to fulfilling the criteria. The characteristic with the lowest score was completeness, i.e. where sufficient data are available to fulfil all the requirements for the model. This is an important characteristic as an incomplete data set could lead to erroneous conclusions being drawn from modelling studies. Thus, the availability of good-quality data is essential to reduce uncertainty when estimating the likelihood of where EID outbreaks may occur and identifying the points on the risk pathway where preventive measures may be taken.

Les facteurs d'émergence sont des éléments ayant le potentiel direct ou indirect d'influencer la probabilité d'émergence ou de réémergence d'une maladie infectieuse. Il est probablement rare qu'une maladie infectieuse émergente apparaisse en raison d'un seul facteur ; c'est plutôt un faisceau de sous-facteurs (éléments pouvant avoir une influence sur un même facteur) qui contribue à ce que les conditions soient réunies pour qu'un agent pathogène puisse (ré)émerger et s'établir. Les concepteurs de modèles ont donc utilisé les données relatives aux sous-facteurs pour identifier les zones sensibles où les prochaines maladies infectieuses émergentes pourraient survenir, ou pour faire une estimation des sous-facteurs ayant la plus grande influence sur la probabilité de leur occurrence. Les chercheurs ont besoin de données de qualité pour décrire ces sous-facteurs, afin de minimiser le risque d'erreur et de biais lors de la modélisation de l'interaction entre les différents sous-facteurs, et de contribuer ainsi à mieux prédire la probabilité d'apparition d'une maladie infectieuse émergente. Les auteurs présentent une étude de cas qui a consisté à évaluer la qualité des données disponibles relatives aux sous-facteurs d'émergence du virus de la fièvre de West Nile au regard de différents critères. Il est apparu que la qualité des données était variable au regard des critères examinés. Le paramètre dont le score était le plus bas est celui de la complétude - le fait que suffisamment de données soient disponibles pour répondre à toutes les exigences du modèle. Il s'agit pourtant d'un paramètre important car des données incomplètes peuvent inciter à tirer des conclusions erronées des études de modélisation. La disponibilité de données de bonne qualité est essentielle pour réduire l'incertitude lors de l'estimation de la probabilité d'apparition de maladies infectieuses émergentes dans des zones déterminées, ainsi que pour identifier les points critiques de concrétisation du risque où des mesures préventives pourraient être mises en place.

Los inductores o factores de inducción [drivers] son aquellos que, directa o indirectamente, pueden influir en la probabilidad de que surjan o resurjan enfermedades infecciosas. Todo indica que rara vez una enfermedad infecciosa emergente aparece por efecto de un solo factor de inducción, sino que es probable que haya más bien una combinación de "subfactores de influencia" [sub-drivers] (factores que pueden influir en un inductor) que cree condiciones propicias para que un patógeno (re)surja y logre asentarse. Los creadores de modelos, por consiguiente, se han servido de datos sobre estos subfactores de influencia para localizar aquellas zonas donde con mayor probabilidad puedan aparecer próximamente enfermedades infecciosas emergentes o para determinar cuáles son los subfactores que más influyen en la probabilidad de que ello ocurra. Para reducir al mínimo los errores y sesgos al modelizar la interacción entre los subfactores y ayudar así a calcular la probabilidad de que surja una enfermedad infecciosa emergente, los investigadores necesitan datos de buena calidad para caracterizar estos subfactores. En el análisis expuesto por los autores se utilizó el virus del Nilo Occidental como ejemplo de estudio para evaluar, con arreglo a diversos criterios, la calidad de los datos existentes sobre los subfactores que inciden en la aparición de este virus. Lo que se constató, en relación con el grado de cumplimiento de los criterios, es que esos datos eran de calidad variable. La característica o parámetro que deparó la puntuación más baja fue la completud, es decir, la existencia de datos suficientes para aportar al modelo toda la información requerida para que este funcione bien. Se trata de una característica importante, pues un conjunto incompleto de datos podría llevar a extraer conclusiones erróneas de los estudios de modelización. Por ello, para reducir la incertidumbre a la hora de calcular la probabilidad de que en cierto lugar surjan brotes de enfermedades infecciosas emergentes y de determinar, dentro de la cadena de materialización del riesgo, aquellos eslabones en los que cabe adoptar medidas preventivas, es indispensable disponer de datos de buena calidad.

Muonic atom spectroscopy with microgram target material.

Muonic atom spectroscopy-the measurement of the x rays emitted during the formation process of a muonic atom-has a long standing history in probing the shape and size of nuclei. In fact, almost all stable elements have been subject to muonic atom spectroscopy measurements and the absolute charge radii extracted from these measurements typically offer the highest accuracy available. However, so far only targets of at least a few hundred milligram could be used as it required to stop a muon beam directly in the target to form the muonic atom. We have developed a new method relying on repeated transfer reactions taking place inside a 100 bar hydrogen gas cell with an admixture of 0.25% deuterium that allows us to drastically reduce the amount of target material needed while still offering an adequate efficiency. Detailed simulations of the transfer reactions match the measured data, suggesting good understanding of the processes taking place inside the gas mixture. As a proof of principle we demonstrate the method with a measurement of the 2p-1s muonic x rays from a 5  µ g gold target.

Evaluation of factors associated with trust in telemedicine in patients with inflammatory bowel disease during COVID-19 pandemic: a multicenter cross-sectional survey.

OBJECTIVE: Telemedicine (TM) has had a powerful impact in recent years, particularly on managing chronic diseases such as inflammatory bowel disease (IBD). Knowing patients' expectations and concerns is essential to increase their confidence in this mode of medical care. PATIENTS AND METHODS: We interviewed a large cohort of IBD patients enrolled at two Italian tertiary referral centers to investigate their trust in TM. RESULTS: A total of 376 patients completed the survey and were included in the study: 293 (77.9%) considered TM valuable for managing their disease, and 307 (85%) wanted to have TM service at their center. However, only 99 patients (26.3%) believed that TM guarantees the same level of care as the in-person visit. Among the socio-demographic variables, those independently associated with trust in TM were the higher education qualification (p=0.02) and the level of competence in information and communication technologies (ICT) (p=0.03). CONCLUSIONS: Our findings highlighted the importance of equipping IBD patients with basic ICT skills to utilize TM services and increase their confidence in ICT with the help of caregivers. Additionally, to improve the perceived value of TM, it will be helpful to use additional tools such as telemonitoring of disease activity using patients' reported outcomes or remote measurement of fecal calprotectin.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Relating SARS-CoV-2 shedding rate in wastewater to daily positive tests data: A consistent model based approach.

During the COVID-19 pandemic, wastewater-based epidemiology (WBE) has been engaged to complement medical surveillance and in some cases to also act as an early diagnosis indicator of viral spreading in the community. Most efforts worldwide by the scientific community and commercial companies focus on the formulation of protocols for SARS-CoV-2 analysis in wastewater and approaches addressing the quantitative relationship between WBE and medical surveillance are lacking. In the present study, a mathematical model is developed which uses as input the number of daily positive medical tests together with the highly non-linear shedding rate curve of individuals to estimate the evolution of global virus shedding rate in wastewater along calendar days. A comprehensive parametric study by the model using as input actual medical surveillance and WBE data for the city of Thessaloniki (~700,000 inhabitants, North Greece) during the outbreak of November 2020 reveals the conditions under which WBE can be used as an early warning tool for predicting pandemic outbreaks. It is shown that early warning capacity is different along the days of an outbreak and depends strongly on the number of days apart between the day of maximum shedding rate of infected individuals in their disease cycle and the day of their medical testing. The present data indicate for Thessaloniki an average early warning capacity of around 2 days. Moreover, the data imply that there exists a proportion between unreported cases (asymptomatic persons with mild symptoms that do not seek medical advice) and reported cases. The proportion increases with the number of reported cases. The early detection capacity of WBE improves substantially in the presence of an increasing number of unreported cases. For Thessaloniki at the peak of the pandemic in mid-November 2020, the number of unreported cases reached a maximum around 4 times the number of reported cases.

Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study.

BACKGROUND: A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. METHODS AND FINDINGS: We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. CONCLUSIONS: Immature CD71+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen.

A physicochemical model for rationalizing SARS-CoV-2 concentration in sewage. Case study: The city of Thessaloniki in Greece.

Detection of SARS-CoV-2 in sewage has been employed by several researchers as an alternative early warning indicator of virus spreading in communities, covering both symptomatic and asymptomatic cases. A factor that can seriously mislead the quantitative measurement of viral copies in sewage is the adsorption of virus fragments onto the highly porous solids suspended in wastewater, making them inaccessible. This depends not only on the available amount of suspended solids, but also on the amount of other dissolved chemicals which may influence the capacity of adsorption. On this account, the present work develops a mathematical framework, at various degrees of spatial complexity, of a physicochemical model that rationalizes the quantitative measurements of total virus fragments in sewage as regards the adsorption of virus onto suspended solids and the effect of dissolved chemicals on it. The city of Thessaloniki in Greece is employed as a convenient case study to determine the values of model variables. The present data indicate the ratio of the specific absorption (UV254/DOC) over the dissolved oxygen (DO) as the parameter with the highest correlation with viral copies. This implies a strong effect on viral inaccessibility in sewage caused (i) by the presence of humic-like substances and (ii) by virus decay due to oxidation and metabolic activity of bacteria. The present results suggest days where many fold corrections in the measurement of viral copies should be applied. As a result, although the detected RNA load in June 2020 is similar to that in April 2020, virus shedding in the city is about 5 times lower in June than in April, in line with the very low SARS-CoV-2 incidence and hospital admissions for COVID-19 in Thessaloniki in June.

Metabolic rejuvenation upgrades circulatory functions of red blood cells stored under blood bank conditions.

BACKGROUND: Red blood cells (RBC) change upon hypothermic conservation, and storage for 6 weeks is associated with the short-term clearance of 15% to 20% of transfused RBCs. Metabolic rejuvenation applied to RBCs before transfusion replenishes energetic sources and reverses most storage-related alterations, but how it impacts RBC circulatory functions has not been fully elucidated. STUDY DESIGN AND METHODS: Six RBC units stored under blood bank conditions were analyzed weekly for 6 weeks and rejuvenated on Day 42 with an adenine-inosine-rich solution. Impact of storage and rejuvenation on adenosine triphosphate (ATP) levels, morphology, accumulation of storage-induced microerythrocytes (SMEs), elongation under an osmotic gradient (by LORRCA), hemolysis, and phosphatidylserine (PS) exposure was evaluated. The impact of rejuvenation on filterability and adhesive properties of stored RBCs was also assessed. RESULTS: Rejuvenation of RBCs restored intracellular ATP to almost normal levels and decreased the PS exposure from 2.78% to 0.41%. Upon rejuvenation, the proportion of SME dropped from 28.2% to 9.5%, while the proportion of normal-shaped RBCs (discocytes and echinocytes 1) increased from 47.7% to 67.1%. In LORCCA experiments, rejuvenation did not modify the capacity of RBCs to elongate and induced a reduction in cell volume. In functional tests, rejuvenation increased RBC filterability in a biomimetic splenic filter (+16%) and prevented their adhesion to endothelial cells (-87%). CONCLUSION: Rejuvenation reduces the proportion of morphologically altered and adhesive RBCs that accumulate during storage. Along with the improvement in their filterability, these data show that rejuvenation improves RBC properties related to their capacity to persist in circulation after transfusion.

Demonstration of Muon-Beam Transverse Phase-Space Compression.

We demonstrate efficient transverse compression of a 12.5 MeV/c muon beam stopped in a helium gas target featuring a vertical density gradient and crossed electric and magnetic fields. The muon stop distribution extending vertically over 14 mm was reduced to a 0.25 mm size (rms) within 3.5 µs. The simulation including cross sections for low-energy µ^{+}-He elastic and charge exchange (µ^{+}↔ muonium) collisions describes the measurements well. By combining the transverse compression stage with a previously demonstrated longitudinal compression stage, we can improve the phase space density of a µ^{+} beam by a factor of 10^{10} with 10^{-3} efficiency.

Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19.

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes. PATIENTS AND METHODS: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint. RESULTS: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint). CONCLUSIONS: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.

SARS-CoV2 RNA detection in a pancreatic pseudocyst sample.

The involvement of gastrointestinal system in SARS-CoV2 related disease, COVID-19, is increasingly recognized. COVID-19 associated pancreatic injury has been suggested, but its correlation with pancreatic disease is still unclear. In this case report, we describe the detection of SARS-CoV2 RNA in a pancreatic pseudocyst fluid sample collected from a patient with SARS-CoV2 associated pneumonia and a pancreatic pseudocyst developed as a complication of an acute edematous pancreatitis. The detection of SARS-CoV2 within the pancreatic collection arise the question of whether this virus has a tropism for pancreatic tissue and whether it plays a role in pancreatic diseases occurrence.

Importation of dengue, Zika and chikungunya infections in Europe: the current situation in Greece.

Although several arboviruses-such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses-are not endemic in Europe, they have the potential to emerge following importation of the virus, taking advantage of the favourable climate and ecosystem. DENV, ZIKV and CHIKV are transmitted by Aedes species mosquitoes and are amongst the most common travel-associated arboviruses. Furthermore, they are linked to sporadic, local outbreaks, especially in the southern parts of Europe. In this review we present in brief the DENV, ZIKV and CHIKV cases imported to Greece during the last 6 years (2013-2018), and we describe the recent laboratory data obtained from the Hellenic Pasteur Institute and the National Reference Centre for Arboviruses. We report 21 imported cases of DENV, ZIKV and CHIKV infections in travellers arriving in Greece. The probable origins were south-eastern Asian (71%) and north-central American (29%) countries. Furthermore, we stress the importance of early and accurate diagnosis in spite of a plethora of diagnostic challenges that clinicians and virologists have to face. Altogether, with the authorities' awareness and the preventive measures to be applied, local transmission events can be successfully avoided, especially in summer when the temperature is favourable for mosquito-borne infections.

Black holes and high levels of neurofilaments in glial fibrillary acidic protein - astrocytopathy: a case report.

BACKGROUND AND PURPOSE: Glial fibrillary acidic protein (GFAP) is an intracellular protein of the astrocytic cytoskeleton. Recently, autoantibodies to GFAP detected by cell-based assay in cerebrospinal fluid (CSF) or serum have been implicated in cerebral astrocytopathy, presenting predominantly with autoimmune meningoencephalomyelitis. However, the phenotypic spectrum, prognosis and therapeutics of this new entity remain to be elucidated. METHODS: Herein, we report radiological, CSF and serological findings during disease exacerbation and remission, from a patient with autoimmune GFAP astrocytopathy, presenting as an immunotherapy responsive GFAP IgG-associated meningoencephalomyelitis. RESULTS: Brain and spine magnetic resonance imaging revealed meningeal enhancement, T2 hyperintensities, black holes, significant sulci widening and spinal atrophy. In addition, high levels of neurofilaments (NfL) and GFAP were also identified during disease exacerbation, consistent with the appearance of the black holes. CONCLUSIONS: To date, black holes and atrophy have never been reported before in autoimmune GFAP astrocytopathy. These findings, combined with the high levels of GFAP and NfL, suggest the existence of an underlying neurodegenerative mechanism in addition to the known inflammatory response. Further studies are needed to elucidate the pathomechanism of GFAP-astrocytopathies.