The medium modulates the medusa effect: Perceived mind in analogue and digital images.

We effortlessly attribute mental states to other people. We also attribute minds to people depicted in pictures, albeit at a reduced strength. Intriguingly, this reduction in intensity continues for images of people within a photograph itself-a phenomenon known as the Medusa effect. The present study replicates the Medusa effect for images shown digitally and on paper. Crucially, we demonstrate that we can reduce the magnitude of the Medusa effect by depicting people digitally within a computer screen (e.g., as if one were interacting with a person on a Zoom call). As well as modulating the quantity of the Medusa effect, changes in pictorial medium can affect the quality of the perceived mind. Specifically, the dimension of Experience-what a depicted person can feel-reflected participants' observations that they could interact with an onscreen person embedded in a digital image. This combination of a robust Medusa effect and the ability to control it both quantitatively and qualitatively opens many avenues for its future application, such as manipulating and measuring mind in immersive media.

Freud's interpretation in "Medusa's Head" and some alternative psychoanalytic implications of Ovid's Medusa.

Freud's very brief 1922 paper on the beheading of Medusa by Perseus wisely concludes with a call for a further examination of the sources of the legend. A now widespread interpretation of this legend is based (often without acknowledgement) on an addition to traditions concerning Medusa made in Ovid's Metamorphoses. It is argued here that this Ovidian innovation has often been misinterpreted, and that a more careful reading of Metamorphoses supports neither a widely alleged exclusively vengeful portrayal of Medusa, nor Freud's portrayal of Medusa's decapitation as solely a pitiable and terrible symbol of castration. Instead, Ovid's complex treatments of myths involving Medusa, Minerva and Perseus present parallels with Kleinian insights into phantasy attacks on fecundity, and into imagined revivals of dead or damaged inside babies. Thus the "displacement upwards" of the fearful castrated maternal genital envisioned in Freud's "Medusa's Head" must stand beside a quite different "displacement upwards" of the life-giving maternal genital. Indeed, tradition holds that Medusa's beheading gives rise to the birth of vigorous twins. Together with allied details, this aligns Ovid's masterwork with theories that modify or displace the so-called "sexual phallic monism" that some believe taints Freud's theories of gender development.

War: Mentalization and Totalitarian State of Mind.

For most residents of Europe, war is a new experience in which they find themselves both as witnesses and participants. In this paper the war in Ukraine serves as an illustration and case example. Like any unfamiliar experience, war elicits profound emotional responses which can be so overwhelming that an individual may be unable to fully process them and to create mental representations of the reality of war. When the psyche becomes entrapped in an unprocessed state, without the capacity to derive meaning from it, this results in the "fossilization" of the psyche akin to what McGinley and Segal describes as a totalitarian state of mind. Subjectivity and individual differences come under collective or personal attack, or both. This state of being prioritizes the needs of the collective psyche over the individual psyche. The image of Gorgon Medusa, who transformed living people into "fossilized" ones, is presented as a metaphor of total identification with the collective dimension. In contrast, the psyche can reveal a creative approach to resolving war-induced trauma. This is depicted in the concept of the Alchemical Stone and its creation, which symbolizes a harmonious connection between the external and internal realms, the subjective and objective experiences, and the real and the imaginal dimension.

Pour la plupart des habitants de l'Europe, la guerre est une nouvelle expérience dans laquelle ils se retrouvent à la fois témoins et participants. Dans cet article, la guerre en Ukraine sert d'illustration et de cas exemplaire. Comme toute expérience qui sort de l'ordinaire, la guerre suscite des réactions émotionnelles profondes qui peuvent être si accablantes qu'un individu peut se trouver incapable de les traiter pleinement et de créer des représentations mentales de la réalité de la guerre. Lorsque la psyché se retrouve piégée dans un état qu'elle ne peut pas traiter, sans la capacité d'en tirer un sens, il en résulte une « fossilisation ¼ de la psyché, semblable à ce que McGinley et Segal a décrit comme un état d'esprit totalitaire. La subjectivité et les différences individuelles font l'objet d'attaques collectives ou personnelles, ou des deux. Cet état d'être donne la priorité aux besoins de la psyché collective plutôt qu'à la psyché individuelle. L'image de la Gorgone Méduse, qui a transformé des êtres vivants en êtres «fossilisés¼, est présentée comme une métaphore de l'identification totale à la dimension collective. En revanche, la psyché peut révéler une approche créative pour résoudre les traumatismes induits par la guerre. Ceci est représenté par le concept de la Pierre Alchimique et de sa création, qui symbolise un lien harmonieux entre les royaumes extérieur et intérieur, les expériences subjectives et objectives, et les dimensions réelles et imaginales.

Para la mayoría de los habitantes de Europa, la guerra es una experiencia nueva en la que se encuentran tanto como testigos y como participantes. En este artículo, la guerra en Ucrania sirve como ilustración y ejemplo de caso. Como cualquier experiencia desconocida, la guerra provoca profundas respuestas emocionales que pueden ser tan abrumadoras que un individuo puede ser incapaz de procesarlas completamente y de crear representaciones mentales de la realidad de la guerra. Cuando la psique queda atrapada en un estado, sin posibilidad de elaborar y sin la capacidad para hallarle un sentido, se produce una "fosilización" de la psique similar a lo que McGinley Segal describe como un estado mental Totalitario. La subjetividad y las diferencias individuales son objeto de ataques colectivos o personales, o ambos. Este estado de ánimo prioriza las necesidades de la psique colectiva sobre la individual. La imagen de la Gorgona Medusa, que transformó a las personas vivas en "fosilizadas", se presenta como una metáfora de la identificación total con la dimensión colectiva. Por el contrario, la psique puede revelar un enfoque creativo para resolver el trauma inducido por la guerra. Esto se representa en el concepto de la Piedra Alquímica y su creación, que simboliza una conexión armoniosa entre los reinos externo e interno, las experiencias subjetivas y objetivas, y las dimensiones real e imaginal.

The Medusa effect: a registered replication report of Will, Merritt, Jenkins and Kingstone (2021).

Will et al.'s (2021 Proc. Natl Acad. Sci. USA 118, e2106640118 (doi:10.1073/pnas.2106640118)) found the Medusa effect, which refers to the tendency that people evaluate a 'person in picture' more mindful than a 'person in picture of a picture'. The present study tried to directly replicate the Experiments 2 and 5 of Will et al.'s (2021), to examine the reliability, validity and generalization of the Medusa effect, as well as its effect on prosocial behaviour. We used the same stimuli and methodology as the original research, but recruited participants in Japan with a larger sample size (N = 1387 in total) as a registered report. In our two replication experiments, we again found that pictures with lower levels of abstraction (L1) were perceived to convey more mind and lead to higher levels of prosocial behaviour, successfully replicating the original findings. The results of the present study suggested the high reproducibility and generalizability of the Medusa effect. Pre-registered Stage 1 protocol: https://osf.io/xj46z (date of in-principle acceptance: 9 February 2023).

Anomalía venosa del desarrollo cerebral trombosada: hallazgos en la resonancia magnética / Developmental cerebral thrombosed venous anomaly: findings in magnetic resonance imaging

Introducción: Las anomalías venosas del desarrollo son las malformaciones vasculares cerebrales más comunes, suelen ser incidentales y benignas, aunque alrededor del 40% se asocian a malformaciones cavernosas, por lo que es esencial buscar otras anomalías vasculares o neurocutáneas asociadas. Caso clínico: Se presenta una mujer de 34 años embarazada que acude por convulsiones y disartria, a la cual se le realiza una resonancia magnética de cráneo urgente. En ella se aprecia el clásico signo de la ‘cabeza de Medusa’, y se concluye como diagnóstico anomalía venosa del desarrollo con trombosis parcial periférica y flujo lento proximal. Conclusiones: La complicación con trombosis de las anomalías venosas del desarrollo es rara y los informes de casos de la bibliografía sugieren que deben manejarse de forma conservadora, como una trombosis del seno venoso, dejando la cirugía para otras complicaciones asociadas. Como radiólogos, debemos conocer las principales características por imagen para elaborar un diagnóstico certero.(AU)

Introduction: Developmental venous anomalies are the most common cerebral vascular malformations. They are usually incidental and benign, although about 40% are associated with cavernous malformations, and so it is essential to look for other associated vascular or neurocutaneous anomalies. Case report: We report the case of a 34-year-old pregnant woman who presented with seizures and dysarthria, and was submitted to an urgent cranial MRI scan. She showed the classic ‘Medusa head’ sign and was diagnosed with developmental venous anomaly with partial peripheral thrombosis and slow proximal flow. Conclusions: Thrombosis rarely occurs as a complication of developmental venous anomalies and case reports in the literature suggest that they should be managed conservatively, leaving surgery for other associated complications. As radiologists, we must be aware of the main imaging features so as to be able to make an accurate.(AU)

Alleviation of ultraviolet-B radiation-induced photoaging using Saussurea medusa Maxim polysaccharide.

Saussurea medusa polysaccharide, the polysaccharide extract of Saussurea medusa Maxim, a traditional Chinese herbal medicine, is used to combat intense ultraviolet radiation, cold, and hypoxia in patients, as well as during drought. This polysaccharide has rich medicinal and ecological values. We aimed to determine whether saussurea medusa polysaccharides can reduce ultraviolet B (UVB)-induced skin photoaging. Seventy-five male Kunming mice were divided into five groups: control, UVB-only, UVB plus vitamin E (VE group), UVB plus saussurea medusa (2 g/kg), and UVB plus saussurea medusa (6 g/kg). The control group was irradiated with normal light, while the other four groups were subcutaneously administered 10 mL/kg/day D-galactose and irradiated with narrow-spectrum UVB for 40 min daily. From day 11, the VE group was administered 0.25 g/kg/day vitamin E, while the saussurea medusa intervention groups were administered 2 and 6 g/kg/day saussurea medusa polysaccharide. After 30 days of continuous administration, treatment with saussurea medusa polysaccharides was found to reduce UVB-induced skin photoaging in mice by elevating the levels of superoxide dismutase, glutathione peroxidase, and hydroxyproline (HYP), while reducing the level of MDA, and inhibiting the EGFR/MEK/ERK/c-Fos pathway. Overall, our findings suggest that treatment with saussurea medusa polysaccharides positively influences skin photoaging.

Reproductive and environmental traits explain the variation in egg size among Medusozoa (Cnidaria).

Medusozoa (Cnidaria) are characterized by diverse life cycles, with different semaphoronts (medusa, medusoid, fixed gonophore, polyp) representing the sexual phase and carrying the gametes. Although egg size is often considered a proxy to understand reproductive and developmental traits of medusozoans, understanding of the processes influencing egg size variation in the group under an evolutionary context is still limited. We carried out a comprehensive review of the variation of egg size in Medusozoa to test whether this variation is related to biological/sexual or environmental traits. Egg size presents a strong phylogenetic signal (λ = 0.79, K = 0.67), explaining why closely related species with different reproductive strategies and different individual sizes have similar egg sizes. However, variation in egg size is influenced by the number of eggs, depth and temperature, with larger eggs frequently present in species with few eggs (1-15), in deep-sea species and in cold-water species. Conversely, the production of small eggs among cold-water species of Staurozoa might be associated with the development of a small benthic larvae in this group. Our study reinforces that egg sizes respond to reproductive and environmental traits, although egg size is highly conserved within medusa classes.

First Atmospheric Measurements and Emission Estimates of HFO-1336mzz(Z).

For the past few years, short-lived unsaturated halocarbons have been marketed as environmentally friendly replacements for long-lived halogenated greenhouse gases and ozone-depleting substances. The phase-in of unsaturated halocarbons for various applications, such as refrigeration and foam blowing, can be tracked by their emergence and increase in the atmosphere. We present the first atmospheric measurements of the hydrofluoroolefin (HFO) HFO-1336mzz(Z) ((Z)-1,1,1,4,4,4-hexafluoro-2-butene, cis-CF3CH═CHCF3), a newly used unsaturated hydrofluorocarbon. HFO-1336mzz(Z) has been detected in >90% of all measurements since 2018 during multi-month campaigns at three Swiss and one Dutch location. Since 2019, it is found in ∼30% of all measurements that run continuously at the Swiss high-altitude Jungfraujoch station. During pollution events, mole fractions of up to ∼10 ppt were observed. Based on our measurements, Swiss and Dutch emissions were estimated at 2-7 Mg yr-1 (2019-2021) and 30 Mg yr-1 (2022), respectively. Modeled spatial emission distributions only partly conform to population density in both countries. Monitoring the presence of new unsaturated halocarbons in the atmosphere is crucial since long-term effects of their degradation products are still debated. Furthermore, the production of HFOs involves climate-active substances, which may leak to the atmosphere─in the case of HFO-1336mzz(Z), for example, the ozone-depleting CFC-113a (CF3CCl3).

Assessment of Genetic Diversity and Genetic Structure of Saussurea medusa (Asteraceae), a "Sky Island" Plant in the Qinghai-Tibet Plateau, Using SRAP Markers.

Saussurea medusa Maxim. is a typical "sky island" species and one with the highest altitude distributions among flowering plants. The present study aimed at analyzing the genetic diversity and population structure of 300 S. medusa accessions collected from 20 populations in the Qilian Mountains in the northeastern Qinghai-Tibet Plateau (QTP), using sequence-related amplified polymorphism (SRAP) markers. A total of 14 SRAP primer combinations were employed to analyze genetic diversity and population structure across all accessions. Out of 511 amplified bands, 496 (97.06%) were polymorphic. The populations in the eastern Qilian Mountains had significantly higher genetic diversity than those in the central and western groups. Population structure analysis revealed greater genetic differentiation among populations with a Gst of 0.4926. UPGMA-based clustering classified the 300 S. medusa accessions into 3 major clusters, while the Bayesian STRUCTURE analysis categorized them into 2 groups. Correlation analyses showed that the genetic affinity of the populations was based on differences in geographical distance, moisture conditions, and photothermal conditions between the habitats. This study represents the first comprehensive genetic assessment of S. medusa and provides important genetic baseline data for the conservation of the species.

I saw Medusa's head sign and turned to stone.

Developmental venous anomalies (DVAs) are characterized by many radially oriented medullary veins surrounding a central draining vessel. When the imaging plane is perpendicular to the central vessel, these medullary veins resemble Medusa's head of snakes. Medusa's head sign, or caput medusae, can be appreciated on contrast enhanced CT scans and MRIs of the brain and is highly indicative of a DVA.

Heterozygous loss-of-function DHX9 variants are associated with neurodevelopmental disorders: Human genetic and experimental evidences.

DExH-box helicases are involved in unwinding of RNA and DNA. Among the 16 DExH-box genes, monoallelic variants of DHX16, DHX30, DHX34, and DHX37 are known to be associated with neurodevelopmental disorders. In particular, DHX30 is well established as a causative gene for neurodevelopmental disorders. Germline variants of DHX9, the closest homolog of DHX30, have not been reported until now as being associated with congenital disorders in humans, except that one de novo heterozygous variant, p.(Arg1052Gln) of the gene was identified during comprehensive screening in a patient with autism; unfortunately, the phenotypic details of this individual are unknown. Herein, we report a patients with a heterozygous de novo missense variant, p.(Gly414Arg) of DHX9 who presented with a short stature, intellectual disability, and ventricular non-compaction cardiomyopathy. The variant was located in the glycine codon of the ATP-binding site, G-C-G-K-T. To assess the pathogenicity of these variants, we generated transgenic Drosophila lines expressing human wild-type and mutant DHX9 proteins: 1) the mutant proteins showed aberrant localization both in the nucleus and the cytoplasm; 2) ectopic expression of wild-type protein in the visual system led to the rough eye phenotype, whereas expression of the mutant proteins had minimal effect; 3) overexpression of the wild-type protein in the retina led to a reduction in axonal numbers, whereas expression of the mutant proteins had a less pronounced effect. Furthermore, in a gene-editing experiment of Dhx9 G416 to R416, corresponding to p.(Gly414Arg) in humans, heterozygous mice showed a reduced body size, reduced emotionality, and cardiac conduction abnormality. In conclusion, we established that heterozygosity for a loss-of-function variant of DHX9 can lead to a new neurodevelopmental disorder.

Trophic Positions of Polyp and Medusa Stages of the Freshwater Jellyfish Craspedacusta sowerbii Based on Stable Isotope Analysis.

When species spread into new regions, competition with native species and predatory-prey relationships play a major role in whether the new species can successfully establish itself in the recipient food web and become invasive. In aquatic habitats, species with a metagenetic life cycle, such as the freshwater jellyfish Craspedacusta with benthic polyps and planktonic medusae, have to meet the requirements of two distinct life stages occurring in two habitats with different food webs. Here, we examined the trophic position of both life stages, known to be predatory, and compared their niches with those of putative native competitors using stable isotope analysis. We found that δ13C and δ15N signatures of medusae overlapped with those of co-occurring Chaoborus larvae and juvenile fish (Rutilus rutilus) in a well-studied lake, implying high competition with these native predators. The comparison of δ15N signatures of Hydra and Craspedacusta polyps in four additional lakes revealed their similar trophic position, matching their predatory lifestyle. However, their δ13C signatures differed not only across all four of the lakes studied but also within one lake over time, suggesting a preference for pelagic or benthic food sources. We conclude that invasive and native polyps differ in their niches due to different food spectra, which favors the invasion success of Craspedacusta.

Correlative Light, Electron Microscopy and Raman Spectroscopy Workflow To Detect and Observe Microplastic Interactions with Whole Jellyfish.

Many researchers have turned their attention to understanding microplastic interaction with marine fauna. Efforts are being made to monitor exposure pathways and concentrations and to assess the impact such interactions may have. To answer these questions, it is important to select appropriate experimental parameters and analytical protocols. This study focuses on medusae of Cassiopea andromeda jellyfish: a unique benthic jellyfish known to favor (sub-)tropical coastal regions which are potentially exposed to plastic waste from land-based sources. Juvenile medusae were exposed to fluorescent poly(ethylene terephthalate) and polypropylene microplastics (<300 µm), resin embedded, and sectioned before analysis with confocal laser scanning microscopy as well as transmission electron microscopy and Raman spectroscopy. Results show that the fluorescent microplastics were stable enough to be detected with the optimized analytical protocol presented and that their observed interaction with medusae occurs in a manner which is likely driven by the microplastic properties (e.g., density and hydrophobicity).

Ingestion, egestion and physiological effects of polystyrene microplastics on the marine jellyfish Rhopilema esculentum.

Jellyfish are planktonic predators that may be susceptible to ingesting microplastics. However, the effects of MP exposure on jellyfish are poorly understood. In this study, the ingestion and egestion of polystyrene microbeads, and its chronic physiological effects on Rhopilema esculentum at an environmental concentration (100 items/L) and a predicted concentration (1000 items/L) were evaluated. The results showed that the ingestion amount of juvenile medusae was relatively low. The MP egestion rates reached 100 % within 9 h of clearance. Chronic exposure (15 days) to MPs at environmental concentrations led to no adverse impacts. Nevertheless, the predicted concentration of MP exposure induced growth inhibition, a reduction in assimilation efficiency, oxygen consumption increase, and lipase enzyme activity reduction in the jellyfish, indicating that MPs can cause adverse effects on the energy budget of jellyfish in the near future. Our study provides new insights into the potential risk of MPs in marine environments.

Comparison of Differences in Chemical Composition and Related Antioxidant Activity of Snow Lotus from Different Origins.

The snow lotus is an endangered traditional Chinese medicinal herb. Saussurea involucrata, Saussurea laniceps, and Saussurea medusa, the three main snow lotus species (five herbs and two S. involucrata cell cultures), were selected for this study. Snow lotus (XLs) was extracted using 75 % (v/v) ethanol. Two reversed phase-high performance liquid chromatography-diode array detector methods were developed and validated for the determination of 10 representative components in XLs. The antioxidant efficacy of XLs and their components was investigated using DPPH, ABTS free radical scavenging, and ROS inhibition experiments. The results showed that the IC50 for DPPH scavenging ranged from 0.06-0.29 mg/mL for XLs and from 0.13-0.63 mg/mL for ABTS, and could downregulate ROS to varying degrees. The results of the antioxidant activity showed that rutin, quercetin, and isochlorogenic acid A contributed to the antioxidant capacity of XLs. The high content and activity of the cell cultures indicate that they can serve as an effective alternative to snow lotus, thus providing a theoretical basis for the selection of herbs and cell cultures to fulfil various needs.

Megastigmane sesquiterpenoids from Saussurea medusa and their anti-inflammatory activities.

Objectives: An ethanol extract of the whole plants of Saussurea medusa had been investigated to find novel anti-inflammatory sesquiterpenoids. Methods: Extensive spectroscopic data and chemical methods were applied to elucidate the structures of the compounds. Results: One new megastigmane sesquiterpenoid (1), along with 11 known analogues (2-12), were obtained from S. medusa. All isolates, except compounds 3 and 6, were mentioned from the studied plant for the first time. Compounds 1, 2, 4, 5, 7, 8 and 12 were firstly isolated from the genus Saussurea. Compounds 2, 9 and 10 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 21.1 ± 1.7 to 46.7 ± 1.9 µM. Furthermore, iNOS expression experiment was performed to examine the interactions between the active compounds and the iNOS enzyme.

Three Pairs of Novel Enantiomeric 8-O-4' Type Neolignans from Saussurea medusa and Their Anti-inflammatory Effects In Vitro.

Three pairs of novel enantiomeric 8-O-4' type neolignans (1a/1b−3a/3b), together with seven known analogues (4−10), were isolated from the whole plants of Saussurea medusa. Their structures were elucidated by extensive spectroscopic data analysis and electric circular dichroism (ECD) calculations after chiral separations. All compounds were obtained from S. medusa for the first time, and compounds 1−3 and 5−10 had never been obtained from the genus Saussurea previously. The anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW 264.7 cells. Compounds (+)-1a, (−)-1b and 5−7 inhibited NO production and had IC50 values ranging from 14.3 ± 1.6 to 41.4 ± 3.1 µM. Compound 7 induced a dose-dependent reduction in the expression of iNOS in LPS-treated RAW 264.7 cells. Molecular docking experiments showed that all active compounds exhibited excellent docking scores (<−7.0 kcal/mol) with iNOS. Therefore, compounds (+)-1a, (−)-1b and 5−7 isolated from the whole plants of S. medusa may have therapeutic potential in inflammatory diseases.

Influences of zinc loads in urban catchment runoff: Roof type, land use type, climate and management strategies.

The contribution of ecotoxic dissolved metals from metallic roofs into urban waterways is a global issue. Identifying the specific origin of dissolved metals is critical to enabling appropriate stormwater management approaches that can provide the intended outcome of cleaner urban waterways. An event load pollutant model, Modelled Estimates of Discharges for Urban Stormwater Assessments (MEDUSA2.0), was used to predict the zinc load contributed from individual roof surfaces, under a wide range of rainfall conditions. Zinc was chosen as the pollutant of most concern given the extensive area of zinc-based roof surfaces, and the prevalence and mobility of zinc within urban waterways. The model categorized each roof by surface material and condition, and was run for individual rain events across multiple years to illustrate the influences on zinc loads from both surface type and rainfall conditions. Scenarios of future management were also assessed through the model to compare their benefits in terms of load reductions against the current baseline loadings. To understand how the load prediction and scenario modelling can provide valuable guidance for stormwater management decision-makers, the model was applied to a large urban catchment in Christchurch, New Zealand. Seven representative subcatchments of the varying proportions of industrial, commercial and residential land use type were also modelled to compare zinc loads generated. Results showed that an individual catchment's composition of roof types was the main driver of zinc load generation rather than the catchment's land use type. The modelled management scenarios demonstrated that reductions of 30% zinc could be achieved by changing only 4-13% of a subcatchment's unpainted zinc-based roof surfaces.

Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)-associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature.

BACKGROUND: In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clinical and paraclinical presentation, tumour association, serological findings, and immunopathogenesis. METHODS: Review of the peer-reviewed and PubMed-listed English language literature on ITPR1-IgG/anti-Sj. In addition, we provide an illustrative report on a new patient with ITPR1-IgG-associated encephalitis with cognitive decline and psychosis. RESULTS: So far, at least 31 patients with serum ITPR1-IgG/anti-Sj have been identified (clinical information available for 21). The most common manifestations were ACA, encephalopathy with seizures, myelopathy, and (radiculo)neuropathy, including autonomic neuropathy. In 45% of cases, an underlying tumour was present, making the condition a facultative paraneoplastic neurological disorder. The neurological syndrome preceded tumour diagnosis in all but one case. In most cases, immunotherapy had only moderate or no effect. The association of ITPR1-IgG/anti-Sj with manifestations other than ACA is corroborated by the case of a 48-year-old woman with high-titre ITPR1-IgG/anti-Sj antibodies and rapid cognitive decline, affecting memory, attention and executive function, and psychotic manifestations, including hallucinations, investigated here in detail. FDG-PET revealed right-temporal glucose hypermetabolism compatible with limbic encephalitis. Interestingly, ITPR1-IgG/anti-Sj mainly belonged to the IgG2 subclass in both serum and cerebrospinal fluid (CSF) in this and further patients, while it was predominantly IgG1 in other patients, including those with more severe outcome, and remained detectable over the entire course of disease. Immunotherapy with intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulins, was repeatedly followed by partial or complete recovery. Long-term treatment with cyclophosphamide was paralleled by relative stabilization, although the patient noted clinical worsening at the end of each treatment cycle. CONCLUSIONS: The spectrum of neurological manifestations associated with ITPR1 autoimmunity is broader than initially thought. Immunotherapy may be effective in some cases. Studies evaluating the frequency of ITPR1-IgG/anti-Sj in patients with cognitive decline and/or psychosis of unknown aetiology are warranted. Tumour screening is essential in patients presenting with ITPR1-IgG/anti-Sj.

Rho GTPase-activating protein 10 (ARHGAP10/GRAF2) is a novel autoantibody target in patients with autoimmune encephalitis.

BACKGROUND: In 2010, we described a novel immunoglobulin G (IgG) autoantibody (termed anti-Ca after the index case) targeting Rho GTPase-activating protein 26 (ARHGAP26, also termed GTPase regulator associated with focal adhesion kinase [GRAF], or oligophrenin-like protein 1 [OPHN1L]) in autoimmune cerebellar ataxia (ACA). Later, ARHGAP26-IgG/anti-Ca was reported in patients with limbic encephalitis/cognitive decline or peripheral neuropathy. In several of the reported cases, the syndrome was associated with cancer. ARHGAP10/GRAF2, which is expressed throughout the central nervous system, shares significant sequence homology with ARHGAP26/GRAF. Mutations in the ARHGAP10 gene have been linked to cognitive and psychiatric symptoms and schizophrenia. OBJECTIVE: To assess whether ARHGAP26-IgG/anti-Ca co-reacts with ARHGAP10. METHODS: Serological testing for ARHGAP10/GRAF2 autoantibodies by recombinant cell-based assays and isotype and IgG subclass analyses. RESULTS: 26/31 serum samples (84%) from 9/12 (75%) ARHGAP26-IgG/anti-Ca-positive patients and 4/6 ARHGAP26-IgG/anti-Ca-positive CSF samples from four patients were positive also for ARHGAP10-IgG. ARHGAP10-IgG (termed anti-Ca2) remained detectable in the long-term (up to 109 months) and belonged mainly to the complement-activating IgG1 subclass. Median ARHGAP26-IgG/anti-Ca and median ARHGAP10-IgG/anti-Ca2 serum titres were 1:3200 and 1:1000, respectively, with extraordinarily high titres in some samples (ARHGAP26-IgG/anti-Ca: up to 1:1000,000; ARHGAP10-IgG: up to 1:32,000). ARHGAP26/anti-Ca serum titres exceeded those of ARHGAP10-IgG in all samples but one. A subset of patients was positive also for ARHGAP10-IgM and ARHGAP10-IgA. CSF/serum ratios and antibody index calculation suggested intrathecal production of ARHGAP26-IgG/anti-Ca and anti-ARHGAP10. Of 101 control samples, 100 were completely negative for ARHGAP10-IgG; a single control sample bound weakly (1:10) to the ARHGAP10-transfected cells. CONCLUSIONS: We demonstrate that a substantial proportion of patients with ARHGAP26-IgG/anti-Ca-positive autoimmune encephalitis co-react with ARHGAP10. Further studies on the clinical and diagnostic implications of ARHGAP10-IgG/anti-Ca2 seropositivity in patients with autoimmune encephalitis are warranted.