PV282 / #36 Case Report Poster Topic:AS03 - Antiphospholipid Syndrome We report a case of a 56-year-old male with a previous history of chronic mild thrombocytopenia, assumed to be a consequence of alcohol consumption (despite the absence of other alcoholic stigmas). He was admitted to the Internal Medicine Department with a 3-month history of extreme fatigue, anorexia, and weight loss (20%). Upon admission, he was hypotensive (100/54mmHg). Blood tests revealed normocytic normochromic anemia (Hb 9.9 g/dL), thrombocytopenia (94 000x10^6/L), elevated activated partial thromboplastin time (76.4s, N 28-40), hyperkaliemia (7.11 mmol/L, N 3.5-5.2) (but normal sodium) and elevated inflammatory parameters (CRP 2.25 mg/dL, ESR 118 mm/h). An extensive workup study was conducted to exclude malignancy and infection. A PET-FDG showed intense uptake in both adrenal glands, with heterogeneity and areas of necrosis, especially in the right adrenal gland (Figure 1A). The endocrinology department was consulted, and hormonal assessments revealed a low serum cortisol (1.9 μg/dL; N 6.2-19.4) and a high adrenocorticotropic hormone (626.0pg/ml; N 7.2-63.3). PAI was assumed and intravenous hydrocortisone (200 mg/day) was started, with subsequent clinical (blood pressure, constitutional symptoms) and laboratory (blood cells count and inflammatory markers) improvement. The main causes for PAI, namely autoimmune Addison’s disease, tuberculosis and human immunodeficiency virus infection, were excluded. At this moment, the Rheumatology department was consulted. Further workup revealed a positive lupus anticoagulant antibody (2 times in 12 weeks apart), ANAs 1/1280 (homogeneous nuclear pattern), anti-dsDNA antibodies elevation (517 UI/mL) and a weekly positive antinucleosome antibody. MRI scans showed atrophy of the adrenal glands (Figure 1B and 1C). The patient was diagnosed with SLE and APS, and after PAI control, he was discharged under glucocorticoid tapering (prednisolone 15 mg/day and fludrocortisone 0.05 mg/day), warfarin and hydroxychloroquine 400mg/day. Later on, azathioprine was also started (100 mg/day) and the patient remained asymptomatic and with normal laboratory parameters. Figure 1 A: PET-FDG at diagnosis moment, showing intense uptake in both adrenal glands; B: abdominal MRI (T2) 3 months after the diagnosis, showing atrophy of both adrenal glands; C: abdominal MRI (T2) 6 months after the diagnosis, showing almost complete disappearance of both adrenal glands, comparing to the previous MRI. Antiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by recurrent arterial, venous and/or microvascular thrombotic events. The disease rarely affects the endocrine system, especially at presentation. The involvement of the adrenal gland, although rare, can be severe. Possible mechanisms behind adrenal manifestations include multiple microthrombosis of the suprarenal vein leading to infarction and adrenal hemorrhage, atrophy and finally failure (primary adrenal insufficiency [PAI]).[1][2] This case illustrates one of the rarest and still most severe consequences of APS. Patients with APS and adrenal hemorrhage, typically have bilateral involvement and develop adrenal insufficiency, just like our patient. [3] The disease can be fatal, thus early diagnosis and treatment as well as a close follow-up and multidisciplinary approach is needed to improve the prognosis of this rare disease.References:[1.] Hochberg MC. Chapter 135: Clinical features of systemic lupus erythematosus. In: Rheumatology 8th Ed. Elsevier;2022:P1113. [2.] Bouki K. Hormones (Athens) 2023;22(3): 521-31. [3.] Meade-Aguilar JA. Clin Immunol 2024;260:109906.

Emotional memories require coordinated activity of the amygdala and hippocampus. Human intracranial recordings have shown that formation of aversive memories involves an amygdala theta-hippocampal gamma phase code. Yet, the mechanisms engaged during translation of aversive experiences into memories and subsequent retrieval remain unclear. Directly recording from human amygdala and hippocampus, here we show that hippocampal gamma activity increases for correctly remembered aversive scenes. Crucially, patterns of amygdala high amplitude gamma activity at encoding are reactivated in the hippocampus, but not amygdala, during both aversive encoding and retrieval. Trial-specific hippocampal gamma patterns showing highest representational similarity with amygdala activity at encoding are reactivated in the hippocampus during aversive retrieval. This reactivation process occurs against a background of gamma activity that is otherwise decorrelated between encoding and retrieval. Thus, phasic hippocampal gamma responses track the retrieval of aversive memories, with activity patterns apparently entrained by the amygdala during encoding.

Memory is typically better for emotional relative to neutral events, a process involving amygdala modulation of hippocampal activity[1][1]–[6][2]. These structures, however, form part of a larger emotional brain network, which in humans includes the temporal pole[7][3], a cortical node whose functional role in emotional cognition remains poorly understood[8][4]–[10][5]. Here, we show, in pharmaco-resistant epilepsy patients performing verbal and visual emotional episodic memory tasks, a selective impairment in recalling verbal emotional memories in left ventral temporal pole (vTP) lesioned patients compared with control patients. Memory for neutral words, and verbal comprehension performance on standard neuropsychological testing, were intact in these patients, indicating absence of general episodic memory or semantic impairment. All patients underwent recordings with intracranial electrodes during memory task performance. Left vTP lesioned patients showed no differences in amygdala or hippocampal electrophysiological responses to emotional words, compared with control patients, putatively isolating a vTP role in emotional memory. Unlike verbal emotional recall, left vTP lesioned patients showed memory enhancement for emotional vs. neutral pictures, whereas two patients with right vTP lesions showed the opposite pattern: impaired memory for emotional pictures but intact verbal emotional memory. These observations establish a critical, lateralized, modality-specific role for human vTP in emotional memory, imply emotional memory deficits in neurological conditions affecting this region, and advance the vTP as a target for neuromodulation in diseases characterized by maladaptive emotional memories. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-2018-COG 819814 Swiss National Science Foundation, SNSF 204651 [1]: #ref-1 [2]: #ref-6 [3]: #ref-7 [4]: #ref-8 [5]: #ref-10

Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case–control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016–2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32–11.28, and 3.64; 95% CI 0.32–41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD.

Understanding how emotional processing modulates learning and memory is crucial for the treatment of neuropsychiatric disorders characterized by emotional memory dysfunction. We investigate how human medial temporal lobe (MTL) neurons support emotional memory by recording spiking activity from the hippocampus, amygdala, and entorhinal cortex during encoding and recognition sessions of an emotional memory task in patients with pharmaco-resistant epilepsy. Our findings reveal distinct representations for both remembered compared to forgotten and emotional compared to neutral scenes in single units and MTL population spiking activity. Additionally, we demonstrate that a distributed network of human MTL neurons exhibiting mixed selectivity on a single-unit level collectively processes emotion and memory as a network, with a small percentage of neurons responding conjointly to emotion and memory. Analyzing spiking activity enables a detailed understanding of the neurophysiological mechanisms underlying emotional memory and could provide insights into how emotion alters memory during healthy and maladaptive learning.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder which may affect the gastrointestinal system. Half of the patients with SLE experience gastrointestinal symptoms, with the most common being nausea, vomiting, anorexia, and abdominal pain. Mesenteric vasculitis is a severe and rare complication of SLE and one of the most frequent causes of severe acute abdominal pain. The authors present a case of a 57-year-old woman with SLE who was diagnosed with necrotizing mesenteric vasculitis following a urinary septic shock. The patient was treated with high-dose corticosteroid therapy and cyclophosphamide, with resolution of the clinical picture.

Emotional memories require coordinated activity of the amygdala and hippocampus. Human intracranial recordings have shown that formation of aversive memories involves an amygdala theta-hippocampal gamma phase code. Yet, the mechanisms engaged during translation of aversive experiences into memories and subsequent retrieval remain unclear. Directly recording from human amygdala and hippocampus, here we show that hippocampal gamma activity increases for correctly remembered aversive scenes, while exerting unidirectional oscillatory influence within the theta/beta frequency range on the amygdala for previously seen aversive scenes. Crucially, patterns of amygdala high amplitude gamma activity at encoding are reactivated in the hippocampus, but not amygdala, during both aversive encoding and retrieval. Trial-specific hippocampal gamma patterns showing highest representational similarity with amygdala activity at encoding are replayed in the hippocampus during aversive retrieval. This reactivation process occurs against a background of gamma activity that is otherwise decorrelated between encoding and retrieval. Thus, retrieval of aversive memories is hippocampal-centered, with hippocampal activity patterns apparently entrained by the amygdala during encoding. ### Competing Interest Statement The authors have declared no competing interest.

Arthritis in the paediatric population is the hallmark of many rheumatic inflammatory diseases, as well as other cutaneous, infectious, or neoplastic conditions. It can be quite devastating, whereby prompt recognition and treatment of these disorders are essential. However, arthritis can sometimes be mistaken for other cutaneous or genetic conditions leading to misdiagnosis and overtreatment. Pachydermodactyly is a rare and benign form of digital fibromatosis, usually manifested by swelling of the proximal interphalangeal joints of both hands, mimicking arthritis. The authors report a case of a 12-year-old boy with a one-year history of painless swelling of the proximal interphalangeal joints of both hands that was referred to the Paediatric Rheumatology department due to the suspicion of juvenile idiopathic arthritis. The diagnostic work-up was unremarkable, and the patient remained asymptomatic over an 18-month follow-up period. A diagnosis of pachydermodactyly was assumed and no treatment was introduced, given the benign nature of the disorder and absence of symptoms. Therefore, it was possible to safely discharge the patient from the Paediatric Rheumatology clinic.

Background Williams syndrome (WS) and Autism Spectrum Disorders (ASD) are neurodevelopmental conditions associated with atypical but opposite face-to-face interactions patterns: WS patients overly stare at others, ASD individuals escape eye contact. Whether these behaviors result from dissociable visual processes within the occipito-temporal pathways is unknown. Using high-density electroencephalography, multivariate signal processing algorithms and a protocol designed to identify and extract evoked activities sensitive to facial cues, we investigated how WS (N = 14), ASD (N = 14) and neurotypical subjects (N = 14) decode the information content of a face stimulus. Results We found two neural components in neurotypical participants, both strongest when the eye region was projected onto the subject's fovea, simulating a direct eye contact situation, and weakest over more distant regions, reaching a minimum when the focused region was outside the stimulus face. The first component peaks at 170 ms, an early signal known to be implicated in low-level face features. The second is identified later, 260 ms post-stimulus onset and is implicated in decoding salient face social cues. Remarkably, both components were found distinctly impaired and preserved in WS and ASD. In WS, we could weakly decode the 170 ms signal based on our regressor relative to facial features, probably due to their relatively poor ability to process faces’ morphology, while the late 260 ms component was highly significant. The reverse pattern was observed in ASD participants who showed neurotypical like early 170 ms evoked activity but impaired late evoked 260 ms signal. Conclusions Our study reveals a dissociation between WS and ASD patients and points at different neural origins for their social impairments.

Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making.

Cat scratch disease (CSD) is a zoonosis caused by Bartonella henselae, which is usually transmitted to humans through scratches or bites from infected cats. It is primarily a disease of children and adolescents, although it can affect individuals of any age. In approximately 10% of cases, patients can present atypical manifestations that may involve the musculoskeletal system. Herein, we report a case of a healthy 51-year-old man that developed low-grade fever and regional lymphadenopathy, followed by erythema nodosum and oligoarthritis. He had been scratched and bitten by his cat before the onset of symptoms. The diagnosis was confirmed serologically by the presence of high titers of specific IgG antibodies. Bartonella henselae was also detected in the blood of the owner's cat by PCR and DNA sequencing.

Clinically amyopathic dermatomyositis (CADM) is a rare condition characterized by dermatomyositis skin lesions without clinically apparent muscle involvement. Respiratory involvement is common, occurring in about half of the cases. Spontaneous pneumomediastinum (PnM) is a rare, and often fatal, complication of CADM. We report a case of a 61-year-old female patient who was diagnosed with anti-melanoma differentiation- associated gene 5 antibody-associated CADM and interstitial lung disease. She developed an extensive spontaneous PnM with subcutaneous emphysema. The patient was treated with a conservative approach which was, initially, successful in reducing the size of the PnM. However, the patient died from an eventual nosocomial pneumonia requiring mechanical ventilation. This case illustrates that improving the management of CADM associated PnM, remains a major unmet need.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.

Introduction: Known risk factors for multiple sclerosis (MS) include smoking, a low vitamin D status, obesity, and EBV, while the inflammatory feature of the disease strongly suggests the presence of additional infectious agents. The association between use of antibiotics and MS risk that could shed light on these factors is still undetermined. We aimed to evaluate the association between antibiotics and MS risk, in the Emilia-Romagna region (RER), Italy. Methods: All adult patients with MS seen at any RER MS center (2015-2017) were eligible. For each of the 877 patients included, clinical information was collected and matched to 5 controls (RER residents) (n = 4,205) based on age, sex, place of residence, and index year. Information on antibiotic prescription was obtained through the linkage with the RER drug prescription database. Results: Exposure to any antibiotic 3 years prior to the index year was associated with an increased MS risk (OR = 1.52; 95% CI = 1.29-1.79). Similar results were found for different classes. No dose-response effect was found. Discussion/Conclusions: Our results suggest an association between the use of antibiotics and MS risk in RER population. However, further epidemiological studies should be done with information on early life and lifestyle factors.

Vaccines are one of the greatest achievements of modern medicine and are safely administered, but they can give rise to autoimmune diseases which include Central Neurvous System or trigger/exacerbate chronic diseases such as multiple sclerosis, neuromyelitis optic and Myelin Oligodendrocyte Glicoprotein Antibody Disease (MOGAD). The SARS-CoV 2 is a human respiratory virus with neuroinvasive and neurotropic capabilities. Several SARS-CoV-2 vaccines have been developed, some with messenger RNA and other with viral vectors. We describe a case of encephalomyelitis with anti-MOG-IgG antibody and recent SARS-CoV-2 vaccine. A 51-year-old woman with no significant medical history presented with acute urinary retention and bilateral hypoesthesia with a T10 sensory level two week after the SARS-CoV-2 vaccine with viral vector. Magnetic resonance imaging showed enhancing T2 hyperintense lesions in the spinal cord with longitudinal extension, in the midbrain and in the optic nerves bilaterally. Serum SARS-CoV-2 IgG anti spike protein was positive (titer was 86 and cutoff 50 UA/ml). Nasopharyngeal SARS-CoV-2 PCR was negative. Cerebrospinal fluid analysis showed lymphocyte pleocytosis (50 cells/μL), negative oligoclonal bands, normal synthesis rate and positivity for anti-MOG-IgG antibody. Borrelia IgM antibodies was positive in serum but Borrelia-PCR was negative in serum and CSF. High dose intravenous methylprednisolone induced clinical improvement. In our patient the SARS-CoV-2 vaccine may have triggered an autoimmune reaction involving the CNS with the production of MOG-IgG antibody, in a patient with genetic susceptibility and transient vaccine-induced immunosuppression. The clinical and strumental follow-up will be necessary to discriminate between a post-vaccination disease or a MOGAD.

Memory for aversive events is central to survival, but can also become maladaptive in psychiatric disorders. Emotional memory relies on the amygdala and hippocampus, but the neural dynamics of their communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, we show that in response to emotionally aversive, but not neutral, visual stimuli, the amygdala transmits unidirectional influence on the hippocampus through theta oscillations. Critically, successful emotional memory encoding depends on the precise amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to ~25-45 milliseconds, a time period that enables lagged coherence between amygdala and downstream hippocampal gamma activity. These results reveal a mechanism whereby amygdala theta phase coordinates transient coherence between amygdala and hippocampal gamma activity to facilitate the encoding of aversive memories in humans.

Although various reports indicated the presence of myalgia in 44–70% and "skeletal muscle injury" (increased CK and myalgia) in 23% of hospitalized patients with SARS-CoV-2 infection, the characterization of neuromuscular involvement is still unsatisfactory, and electrophysiologic studies have rarely been performed. We describe a case of acute myopathy at onset of SARS-CoV-2 infection. A 73-year-old woman, with post-infarct ischemic heart disease in her medical history, presented with progressive weakness in the lower limbs and pain, without fever. On admission, neurological examination showed proximal tetraparesis, prevalent in the lower limbs, and reflexes were diminished. CK in the serum was to >6000 U/L (normal value 10–145 U/L), hepatic enzymes were elevated (GOT 814 U/L, n.v.1–31), urin Hb > 1 (n.v. absent).Polymerase chain reaction (PCR) testing for SARS-COV-2 was positive. Chest X-ray showed right lower patchy opacities, but oxygen saturation was 94% on room air. Motor nerve conduction studies (NCS) showed mild sensory polyneuropathy; the needle electromyography (EMG) demonstrated myopathic abnormalities with fibrillation potentials in the lower limbs, rapid recruitment on interference pattern and reduced compound muscle action potential amplitude. The therapy with high dose of steroids induced significative clinical improvement. In two weeks, CK levels almost normalized and the patient recovered the ability to walk with assistance. The severe immune activation known to occur in COVID-19 patients probably plays an important pathophysiological role for onset of rhabdomyolysis, but further studies are needed to elucidate the mechanisms, appropriate treatment, and long-term clinical outcomes of muscular manifestations associated with COVID-19 disease.

Seroprevalence studies are crucial both for estimating the prevalence of SARS-CoV-2 exposure and to provide a measure for the efficiency of the confinement measures. Portuguese universities were closed on March 16th 2020, when Portugal only registered 62 SARS-CoV-2 infection cases per million. We have validated a SARS-CoV-2 ELISA assay to a stabilized full-length spike protein using 216 pre-pandemic and 19 molecularly diagnosed SARS-CoV-2 positive individual's samples. At NOVA University of Lisbon, presential work was partially resumed on May 25th with staggered schedules. From June 15th to 30th, 3–4 weeks after the easing of confinement measures, we screened 1,636 collaborators of NOVA university of Lisbon for the presence of SARS-CoV-2 spike specific IgA and IgG antibodies. We found that spike-specific IgG in 50 of 1,636 participants (3.0%), none of which had anti-spike IgA antibodies. As participants self-reported as asymptomatic or paucisymptomatic, our study also provides a measurement of the prevalence of asymptomatic/paucisymptomatic SARS-CoV-2 infections. Our study suggests that essential workers have a 2-fold increase in viral exposure, when compared to non-essential workers that observed confinement. Additional serological surveys in different population subgroups will paint a broader picture of the effect of the confinement measures in the broader community.