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P11. In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer's Disease Patients

Simone D'Angiolini1, Emanuela Mazzon1, Agnese Gugliandolo1

1 IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles in the brain. Interestingly, the role of cerebellum in AD pathogenesis is not clear yet, even if it is known that Aβplaques appear in the cerebellum in late stages of the disease, suggesting that it can be resistant to specific neurodegenerative mechanisms. We performed an in silico analysis to evaluate the transcriptional profile of cerebellum in AD patients and non-AD subjects in order to deepen the knowledge on cerebellum role in AD. The analysis highlights that only the molecular function (MF) “active ion transmembrane transporter activity” was overrepresented. This MF included 21 differentially expressed genes (DEGs). Some of them may be involved in the ion dyshomeostasisreported in AD. Other DEGs assumed in the cerebellum an opposite regulation compared to those reported in other brain regions in AD patients. They may be associated to a protective phenotype, that may explain the initial resistance of cerebellum to neurodegeneration in AD. Of note, this MF was not overrepresented in prefrontal cortex and visual cortex indicating that it represents a peculiarity of the cerebellum.

P25. APOE methylation patterns is associated with genotype in blood and brain from Alzheimer’s disease patients

Di Gerlando Rosalinda1,2, Rizzo Bartolo1,2, Dragoni Francesca 1,2, Ferrari Riccardo Rocco1,3, Davin Annalisa3, Poloni Tino Emanuele3, Costa Alfredo2, Cotta Ramusino Matteo2, Perini Giulia2, Stefano Cappa2,4, Gagliardi Stella2

1 University of Pavia, Pavia, Italy
2 Dementia Research Center, IRCCS Mondino Foundation, Pavia, Italy.
3 Golgi-Cenci Foundation, Abbiategrasso, Italy
4 ICoN Cognitive Neuroscience Center, Institute for Advanced Studies, IUSS, Pavia, Italy

APOE is the major genetic risk factor for sporadic Alzheimer’s Disease (AD), and the carriage of APOEɛ4 allele increases the risk to develop AD, especially in homozygosis. We used both peripheral blood mononuclear cells (PBMCs) and hippocampus samples to determine the methylation of two putative differentially methylated regions (DMRI and DMRII) at the 5’UTR of APOE with the aim to identify possible differentially methylated CpG sites and to associate these with the genotype and age.
PBMCs were isolated from blood samples of 20 AD and 20 healthy controls (HC). 6 AD and 3 HC hippocampus samples were provided by Golgi Cenci Foundation. DNA was extracted and after bisulfite conversion, the two regions of interest were amplified using PyroMark PCR (Qiagen) with custom designed primers and then sequenced on a PyroMark Q48 instrument (Qiagen).
In AD PBMCs and hippocampus samples we found that site 2 and 3 for DMRI and site 5 and 6 for DMRII showed a higher methylation level than HC. In PBMCs, AD patients with ɛ3/ɛ4 genotype showed a higher methylation level in both DMRI and DMRII regions with respect to HC. Finally, in AD PBMCs and hippocampus, age progression was associated to an increase in the methylation level of DMRI, contrary to HC that showed an opposite trend.
In conclusions, our data suggest the presence of a mild difference in methylation in APOE 5’UTR at least in PBMCs of AD patients which seems to be associated also to ɛ3/ɛ4 genotype and age.

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EPILESSIA

P64. A multidisciplinary approach combining clinical and molecular genetics with functional studies: DEE patient-based models.

Antonio Falace1, Antonella Riva1, Ganna Balagura1, Greta Volpedo1, Marcello Scala2, Paolo Scudieri2,3, Simona Baldassari2, Federico Zara2 ,3, Pasquale Striano1,3

1 Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa
2 Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa
3 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa

Developmental and epileptic encephalopathies (DEE) are a group of severe disorders of early life, characterized by epilepsy, developmental brain dysfunction and often accompanying intellectual disability, behavioural abnormalities, and motor dysfunction. The number of known monogenic determinants underlying DEE is growing and provides neurobiological insights for convergence in the mechanistic pathways, essential to improve the outcome of these devastating disorders, for which no specific treatment options are available. Indeed, hundreds of causative mutations in several genes associated with DEEs are involved in different neuronal functions, especially in synaptic development and plasticity. Functional and molecular studies elucidating how different mutations can disturb the converging pathways can lead to identifying potential targets, thereby opening perspectives for future treatment. For this purpose, in the last years, we have developed a multidisciplinary approach combining clinical and molecular genetics with functional studies based on patient-based models. We assembled a cohort of patients harboring de novo or biallelic variants in synaptic genes presenting with a severe DEE and iPSCs-derived neuronal cells were developed for a subgroup of them. We will investigate the morpho-functional phenotype of neuronal cells derived from the patient’s cells to provide functional evidence of the pathogenicity of identified variants and to dissect the physiopathological molecular basis involved. Identifying common dysfunctional pathways our approaches aim to provide the first step toward preclinical studies to envisage specific therapeutic targets and personalized treatment options for DEE.

P65. ENCefalopatia Acuta Non reversibile del paziente in Terapia intensivA (studio ENCANTA)

Merli Elena, Contardi Sara, D’Angelo Roberto, Guarino Maria, Zini Andrea

Introduction: the long-term health status of intensive care unit (ICU) survivors has become an increasing concern in recent years and cognitive impairment is often considered to be the heaviest burden of illness. The term Critical Illness (CI) includes the set of pathological states determined by intensive care and hospitalization in the ICU. The involvement of the central nervous system has been less studied in the neurological field. It is known that it is more frequent in patients with delirium and determines long-term outcomes such as a multidomain cognitive deficit in 6-40% of cases (Pandharipande, 2013).
Materials e methods: a) Firstly, we performed a systematic review of the literature concerning the prevalence of development of cognitive deficit after ICU. We followed PRISMA guidelines (Mother et al, 2015). It was conducted on MEDLINE (Pubmed), Google scholar, Embase, between 1/1/1965 and 11/3/2023. The terms of the research included: (i) cognitive impairment (“dementia”[MeSH Terms] OR “dementia”[All Fields] OR “dementias”[All Fields] OR “dementia s”[All Fields] OR “cognitive dysfunction”[All Fields] OR “cognitive decline”[All Fields] OR “cognitive impairment”[All Fields]), (ii) critical illness (“critical illness”[All Fields]). b) Secondly, we started a prospective observational study, including patient in ICU with no disabilities or neurological diseases, in order to verify the prevalence of cognitive impairment and identify clinical, laboratory and EEG predictive markers.
Results: a) Studies included in the revision.

Conclusions: the integrated neurological evaluation of patients in ICU could be of useful in defining the prognosis in terms of cognitive outcomes. To this end, the research and identification of early clinical, biological and neurophysiological markers would be of great interest and a possible objective of future studies.

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MALATTIE CEREBROVASCOLARI

P72. Is Erenumab effective and safe in long term migraine treatment? A three-years observational study

Elisa Maria Bruno, Davide Mascarella, Valentina Favoni, Giulia Pierangeli, Sabina Cevoli

Background: Erenumab has proven to be a highly effective and well tolerated Migraine preventive medication since its approval in 2018. Although the abundant real-world scientific production on this topic confirmed long-term tolerability, most studies have relatively short follow-up. Hence, longer follow-up data with a high level of surveillance for efficacy and safety are warranted in a potential life-long using medication.

Methods: This observational prospective study included all patients with a diagnosis of Episodic or Chronic Migraine who started treatment with Erenumab between May-2019 to August-2020. Patients were followed up with a minimum of two outpatients’ evaluations per year and for a total duration of three years. Mean Headache days (MHD) were collected throughout the study period as well as adverse events.

Results: A total of 164 patients were included. After the first year of treatment, 34% of the total cohort showed a sustained reduction of at least 50% (50%RR) in MHD and 84/164(50.9%) continued the treatment. Three patients dropped-out due to side effects (1.8% of the total cohort) whereas 23/164 patients dropped-out due to inefficacy. During the subsequent therapy cycles, we observed a relative stabilization of dropouts (64/84 patients started the 3rd cycle) and a slight relative increase in 50% responders (50.9% 1° cycle, 55%3° cycle). No baseline feature was predictive of long-term response.

Conclusions: We observed a halving of the treated patients at 1 year, followed by a stabilization of dropouts and a ‘selection’ of the most responsive patients, with a very high 50%RR at the end of the third year.

P770. Investigating Temporal Muscle Thickness (TMT) as a predictor of functional outcome after acute ischemic stroke treatment

B. Ravera1, C. Lombardi1, I. Scala1, S. Bellavia1, P. Rizzo1, G. Frisullo2, A. Broccolini2, G. Della Marca2, M. Monforte2

1 UOC Neurologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy ,
2 UOC Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;

Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients at risk of sarcopenia, a major cause of disability and frailty, especially among the elderly. Reliability of TMT as a tool to identify sarcopenia has been confirmed in a mixed stroke population (ischemic and hemorrhagic) but there isn’t available data regarding its relationship with ischemic stroke outcome after acute phase treatment.

TMT of patients who underwent revascularization was measured on brain CT images acquired upon arrival in the ER. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. Patients were further divided into two groups: at-risk vs not-at-risk of sarcopenia based on a literature cut-off of mean TMT. Univariate and multivariate analyses were performed to assess the significance of mean TMT as predictor of functional outcome.

Patients with unfavorable outcomes at 90 days (mRS > 3) had lower values of mean TMT (4.9 vs 5.6 mm, p=0.02), as well as the subgroup of patients who passed away (4.1 vs 5.6 mm, p <0.001). In the multivariate analysis, neither mean TMT nor belonging to the at-risk of sarcopenia group were confirmed as independently associated with worse outcomes.

A trend in higher frequencies of very severe outcomes for patients at-risk of sarcopenia undergoing revascularization treatments for acute ischemic stroke was identified. Actual evidence fully supports treatment of this frail population according to established guidelines. Further investigations are needed to verify if sarcopenia may be an independent prognostic factor.

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MALATTIE RARE

P88. Bevacizumab in Leukoencephalopathy with Calcifications and Cysts: Clinical and neuroradiological longitudinal follow-up

Bianca Buchignani1,2*, Elena Scaffei1,3*, Rosa Pasquariello1, Paola Cristofani 1, Raffaello Canapicchi1, Laura Biagi1, Flavio Giordano 3,4 Emanuela De Marco5, Yanick J. Crow6,7 , Roberta Battini1,8

1 Department of Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
2. Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy
3 Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, Florence, Italy
4 Department of Neurosurgery, Meyer Children's Hospital IRCCS – Italy
5 Paediatric Oncology and Haematology Department, Santa Chiara Hospital, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
6 MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
7 Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Paris Descartes University, Paris, France
8 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

* These authors contributed equally to this work and share first authorship

Leukoencephalopathy with Calcifications and Cysts (LCC) is a rare genetic disease caused by biallelic mutations in SNORD118. From a pathological point of view, LCC is an exclusively neurological microangiopathy, and it is often diagnosed using brain magnetic resonance imaging due to the highly characteristic triad of leukoencephalopathy, intracranial calcifications, and brain cysts. Age at onset, presentation and disease evolution are variable, ranging from a pauci-symptomatic disease to the rapid evolution of signs and symptoms with loss of motor and cognitive abilities. No therapies specific for LCC are currently available. However, according to the literature, bevacizumab might represent an effective modality to improve the clinical and MRI features of the disease. Still, uncertainty remains as to the true efficacy of this approach, when to begin therapy, appropriate dosing, and the consequences of drug withdrawal. We describe the long-term clinical and neuro-radiological follow-up of a 10-year-old child with LCC which was treated with bevacizumab from the age of ten years old. We report disease evolution and neuroimaging following repeated cycles of treatment with bevacizumab. This case report suggests that repeated cycles of bevacizumab might effectively modify disease progression, possibly indicating a time-dependent effect and paves the way to the need of the collection of data in a centralized registry to improve the description of the natural history of LCC.

P91. Evaluation of a gene therapy-based approach for the treatment of CMT2A

Elena Abati1,2, Silvia Bono2, Marc-David Ruepp3, Sabrina Salani2, Linda Ottoboni2, Valentina Melzi2, Chiara Cordiglieri4, Sabrina Pagliarani1, Roberta De Gioia2, Alessia Anastasia2, Michela Taiana2, Manuela Garbellini2, Simona Lodato5,6, Paolo Kunderfranco5,6, Daniele Cazzato7, Daniele Cartelli7, Caterina Lonati8, Nereo Bresolin 1,2, Giacomo Comi1,2, Monica Nizzardo1,2, Stefania Corti1,2, Federica Rizzo1,2

1 Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
2 IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
3 United Kingdom Dementia Research Institute Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK
4 Istituto di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.
5 Humanitas University, Department of Biomedical Sciences, 20072 Pieve Emanuele (Milan), Italy.
6 IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy.
7 Fondazione IRCCS Istituto Neurologico Carlo Besta.
8 Center for Preclinical Research, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Pace 9, 20100 Milan, Italy.

Introduction: Charcot–Marie–Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. Here we propose a novel potential therapeutic approach combining RNA interference and gene therapy.

Methods: We characterized a cohort of thirteen patients from ten families and obtained induced pluripotent stem cells (iPSCs) from two siblings with p.A383V mutation. We differentiated iPSCs into spinal motor neurons (MNs) and evaluated our strategy both in vitro, in our IPSC-based MNs, and in vivo, in a CMT2A transgenic mouse model.

Results: Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E, in a carrier with a severe sensorimotor axonal neuropathy. Our therapeutic approach significantly rescues the CMT2A MN phenotype in vitro, stabilizing the altered axonal mitochondrial distribution and correcting abnormal mitophagic processes, and allows proper MFN2 molecular correction in CMT2A mice.

Conclusions: In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. In addition, we demonstrate the feasibility of a gene therapy-based approach for treating CMT2A, proving its effectiveness in vitro and in vivo.

P920. Molecular testing implementation and screening of Italian cohorts for GAA-FGF14 ataxia (SCA27B)

Rossi Salvatore1, Lo Vecchio Filomena2, Pomponi Maria Grazia2, Tabolacci Elisabetta3, Genovese Danilo1, Di Lazzaro Giulia4, Santorelli Filippo5, Genuardi Maurizio2,3, Silvestri Gabriella1,4

1Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
2UOC Genetica Medica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
3Dipartimento Universitario Scienze Della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, Roma, Italy
4UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
5Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Calambrone, Italy

Introduction: Notwithstanding recent advances in genetics, a large proportion of patients with degenerative ataxia remains undiagnosed, especially late-onset cerebellar ataxias (LOCA) cases. Recently, SCA27B, an autosomal-dominant (AD) LOCA with episodic features, was found to be caused by an intronic GAA repeat expansion (RE) in FGF14, accounting for 10-61% of unsolved LOCA cases in different cohorts. We therefore decided: i) to implement the molecular technique to detect the FGF14 RE to be available in clinical-diagnostic settings, and ii) to screen for SCA27B a cohort of unsolved ataxia cases.

Methods: We implemented a standard PCR (sPCR) to rapidly rule out non-affected patients, and used a combination of long-range PCR (LR-PCR) and repeat-primed PCR (RP-PCR) to diagnose SCA27B. Sizing was performed both by capillary and gel electrophoresis on LR-PCR products. We tested this workflow on 63 patients with diagnosis of cerebellar ataxia (CA, 51 sporadic cases and 12 with a likely AD inheritance pattern), 21 Multiple System Atrophy type C (MSA-c) patients, 7 patients with tremor, 49 patients with parkinsonism, and 35 controls.

Results: Overall, our workflow allowed us to find 8 SCA27B out of 176 subjects (4.5%) and further 4 patients among their relatives, for a total of 12 patients. The estimated prevalence was 6.3% among CA patients (4/63), 4.8% in MSA-c (1/21), 14.3% among patients with tremor (1/7), 2% among patients with parkinsonism (1/49), and 2.8% among controls (1/35). Considering only AD-CA cases, we found a higher prevalence of SCA27B patients (3/12, 25%). Sizing of the FGF14 RE was more accurate by gel electrophoresis.

Conclusions: Our workflow is accurate for the use in clinical-diagnostic settings. SCA27B is a frequent cause of LOCA also in the Italian population, and we further expanded its phenotype, including also tremor, parkinsonism, and dystonia among clinical features.

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NEUROONCOLOGIA

P1060. Epilessia all’esordio clinico nei pazienti con glioblastoma: quale ruolo nella prognosi?

J. Rossi1,2, N. Biagioli3, F. Cavallieri2, R. Rizzi2, M. Russo2, M. Bondavalli2, G. Toschi2, G. Biagini3, A. Pisanello2, F. Valzania2

1 Programma di Dottorato in Medicina Clinica e Sperimentale, Università di Modena e Reggio Emilia, Modena
2 S.C. di Neurologia, Dipartimento Neuromotorio e Riabilitativo, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
3 Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emila, Modena

Razionale e obiettivi
L’epilessia può manifestarsi nel 29-52% dei pazienti con glioblastoma (GBM). Alcune evidenze attuali suggeriscono un ruolo prognostico favorevole delle crisi epilettiche all’esordio nei pazienti con GBM. Tuttavia, alcuni fattori confondenti sono emersi dagli studi precedenti, tra cui l’eterogeneità dei pazienti in termini di localizzazione del tumore, caratteristiche biomolecolari e regimi di trattamento antitumorale. Pertanto, ci siamo proposti di studiare le differenze in termini di sopravvivenza globale (OS) e libera da progressione (PFS) tra i partecipanti con e senza epilessia all’esordio clinico in una popolazione di pazienti con GBM.

Metodi
Riportiamo i dati preliminari di uno studio retrospettivo monocentrico, nel quale sono stati analizzati consecutivamente 31 pazienti con diagnosi di GBM sopratentoriale. Di questi, 12 pazienti hanno sviluppato epilessia prima dell’intervento neurochirurgico e 19 pazienti non hanno presentato crisi epilettiche. Tutti i pazienti sono stati sottoposti ad asportazione macroscopicamente totale del tumore, seguita da radioterapia e chemioterapia concomitante con temozolomide (TMZ) secondo lo schema STUPP, e da almeno sei cicli di chemioterapia adiuvante con TMZ.

Risultati
Nella nostra popolazione non sono state al momento riscontrate differenze in termini di OS e PFS tra i partecipanti con e senza epilessia all’esordio clinico.

Conclusioni
I dati ottenuti al momento potrebbero essere limitati dalla ridotta dimensione campionaria. Il vantaggio di questo studio è l’attenta selezione dei pazienti e l’utilizzo della nuova classificazione WHO del 2021.

P1061. Rehabilitation in adult and pediatric neuro-oncology: a survey on current practices and challenges

Giulia Berzero, Angela Mastronuzzi, Enrico Franceschi, Claudia Milanaccio, Elisa Bennicelli, Massimo Filippi, Pierfranco Conte, Antonio Silvani, Andrea Pace

Background: Adult and pediatric patients affected with brain tumors experience significant disability throughout their course of disease. Although rehabilitation represents a fundamental part of integrated care, it still exists substantial heterogeneity on how rehabilitation needs are fulfilled across the national territory, hampering to reach a consensus in this area.

Objectives: In 2023, a working group on Neurorehabilitation was created within the Virtual Institute of Neuro-Oncology (VINO) of the RIN to boost the research in this domain. The first initiative of the working group was to gather information on existing practices with the final aim to build a common ground for future projects.

Materials and methods: Between June and August 2023, a survey on neurorehabilitation practices and facilities was created and disseminated among the IRCCS participating to the VINO.

Results: Eight IRCCS completed the survey, including two pediatric and six adult centers. The two pediatric centers (Ospedale Pediatrico Bambin Gesù, Istituto Giannina Gaslini) proved to be similarly equipped, disposing of both inpatient and outpatient rehabilitation programs counting on tools including telerehabilitation and robotics. A higher degree of heterogeneity was noticed among the six adult centers (Istituto Scienze Neurologiche, Ospedale San Martino, Istituto Carlo Besta, IRCCS San Camillo, Ospedale San Raffaele, Istituto Regina Elena), in which inpatient rehabilitation units, telerehabilitation/robotics, and home rehabilitation programs were not universally available.

Conclusions: The present survey confirms a substantial heterogeneity on current resources and practices on rehabilitation and highlights points of improvement that could be the object of a consensus and of specific studies.

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PARKINSON E DISORDINI DEL MOVIMENTO

P133. Automated tablet scoring of Rey Complex figure in PD patients: differences between spatial, cinematic and procedural abilities

Silvia Gobbo1, Marco Petilli2, Marco Rabuffetti1, Roberta Daini1,2 & Francesca Lea Saibene1

1 IRCCS Fondazione don Carlo Gnocchi ONLUS
2 Università degli studi di Milano-Bicocca

A commonly used test to assess visuo-constructional skills is the copy of Rey-Osterreith Complex figure (RCF). However, its scoring is solely based on the accuracy of the graphical output not allowing for a quantitative assessment of other abilities involved as motor and procedural skills. This represents a limitation in the assessment of patients, especially those affected by Parkinson’s Disease (PD). This because they do not show a deficit limited to accuracy, but show visuomotor delay and an altered copy procedure. To overcome this limitation, a tablet method for scoring RCF (TRCF) was developed. It allows to extract quantitative indexes about a spatial (SPA), a procedural (PRO), and a kinematic (KIN) performance in RCF copy and recall. In the present study we administered the TRFC to PD patients, a group of control patients (with right acquired lesion), or to healthy controls (HC). We aimed at investigating the ability of the TRFC to discriminate the three indexes in the three groups. Results reveal that the KIN index is the most impaired in PD patients, while the SPA index is the most impaired in the control patients. No differences between the indexes are observed in the HCs. In addition, both KIN and SPA indexes are able to discriminate between PD patients and HCs and between PD and control patients. These results confirm the usefulness of TRFC in PD patients: it allows not only to describe their performance in greater detail, but also to discriminate PD patients from other categories of patients.

P1330. Gender Differences and Cognitive Reserve in People with Parkinson’s Disease: possible interactions and effects on cognitive domains

Anna Salvatore1, Sonia Di Tella1,2, Pietro Arcuri1, Anna Castagna1, Elisabetta Farina1, Margherita Alberoni1, Elena Calabrese1, Jorge Navarro1, Mario Meloni1,3 and Francesca Lea Saibene1

1 IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
2 Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy
3 UOC Neurologia, Azienda Ospedaliero-Universitaria, Cagliari, Italy

Several studies investigated gender differences (GDs) and cognitive reserve (CR) in people with Parkinson’s disease (PwPD). The aim of this study was to investigate the effects of gender and the impact of CR on cognitive functioning in PwPD.
70 PwPD (Age:70.17±6.61; H&Y:1.50-3; 37M/33F). Cognitive functioning was assessed through the administration of a global cognitive functioning test (MoCA Test) and a complete neuropsychological battery while CR was investigated through the CRI-q.
PwPD with higher-CR showed a significantly better performance compared with PwPD with lower-CR in the following tests: MoCA Test, Alternating Verbal Fluency, Raven’s Matrices, Digit Span Backward, Copy and Recall of Rey’s Figure and Imitation Gesture Test. Furthermore, a significant interaction effect was found between Gender*CR: females with higher-CR show a better performance than females with lower-CR in a verbal attentional shifting task. This wasn’t observed in males. Sample was divided in two groups by the median of the CR. Non-parametric analyses showed an effect of CR, in addition to the above-mentioned, also in the following tests: CDT, FAB, TMT-B, TMT B-A and Phonemic Verbal Fluency while it wasn’t replicated in the MoCA Test and in Alternating Verbal Fluency test. In particular, results showed that women with higher-CR, unlike men, performed better than females with lower-CR.
In conclusion, CR has a positive impact on several cognitive domains, especially in females. Thus, high CR may help to cope with initial cognitive difficulties in PwPD. Further studies are necessary to investigate how CR and GDs modulate cognitive impairment in PwPD.

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NEURORIABILITAZIONE

P138. ADVANCED ANALYSIS OF INERTIAL SENSOR-BASED TIMED UP AND GO TEST AND SELF-PACED TREADMILL-TO-OVERGROUND GAIT COMPARISON

Daniele Emedoli1, Federico Colombo2 , Nicolò Domenichetti2 , Luigi Albano3 , Filippo Agnesi4 , Andrea Bandini4 , Elena Losanno4 , Simone Romeni5 , Federica Alemanno1 , Elise Houdayer1 , Filippo Gasperotti1 , Andrea Tettamanti1 , Solaiman Shokur5 , Silvestro Micera4,5, Pietro Mortini3, Sandro Iannaccone1

1 Department of Rehabilitation and Functional Recovery, IRCCS Ospedale San Raffaele, Milan
2 Student, Vita-Salute San Raffaele University, Milan
3 Neurosurgery and Gamma Knife Unit, IRCCS Ospedale San Raffaele, Milan
4 The BioRobotics Institute, Interdisciplinary Health Center, and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa
5 Bertarelli Foundation Chair in Translational Neuroengineering, Neuro-X Institute, School of Engineering, Ecole Polytechnique Federale de Lausanne (EPFL)

INTRODUCTION. The application of Inertial Measurement Units during the Timed Up and Go (TUG) test has been introduced, allowing the identification of postural transitions and different subphases. In the meantime, the development of self-paced treadmill expands the possibilities for studying and assessing mobility.

AIMS. The aims of the study were to: (i) compare duration of different subphases of TUG between healthy and pathological subject; (ii) compare gait parameters during overground walking with those obtained during selfpaced treadmill walking in semi-immersive and fully immersive virtual reality (VR) environments.

MATERIALS AND METHODS. 48 participants were grouped as: 29 healthy subjects, 12 Parkinson’s Disease patients and 7 Stroke patients. Three TUG and 120 steps at spontaneous speed were obtained overground, with self-paced treadmill walking in semi-immersive and fully immersive VR environments.


RESULTS. The comparative analyses between healthy controls and patients showed statistically significant differences for total TUG time and subphases. When comparing gait parameters across overground walking, self-paced treadmill semi-immersive VR, and immersive VR, it was found that most of the variables showed no statistically significant differences.

CONCLUSIONS. The results suggest that TUG measurements may provide a more accurate assessment of functional mobility in patients. Also, results regarding the comparison of gait parameters indicate that locomotion on self-paced treadmill is similar to overground walking, suggesting the opportunity for gait training and the implementation of rehabilitation scenarios in a virtual reality environment.

P1621. Effects of a virtual reality rehabilitation protocol for sensorimotor and proprioception deficit in patients after stroke.

Giada Lullini, Sara Castaldini, Sara Ventura, Annalisa di Gioia, Elisabetta Magni, Andrea Turolla, Alessia Tessari

Upper limb motor impairment is one of main disabilities after stroke. Deficits in proprioception and body representations can impair motor, kinesthetic, and perceptual control. Recent studies demonstrate that the paradigm of the illusion of the bodily self improves the rehabilitation of the injured limb. Virtual reality takes on an increasingly important role, allowing the illusion of the bodily self to be implemented thanks to biofeedback and personalization of rehabilitation protocols. The objective of this study is to evaluate effects of a neurorehabilitation protocol with a virtual reality system for the recovery of sensorimotor and proprioceptive deficit of the upper limb in patients with stroke outcomes and compare the latter to usual care rehabilitation protocol.
30 patients with sensorimotor and proprioceptive upper limb disfunction after stroke were included and randomized into two groups: one group performed the neurorehabilitation protocol via virtual reality using the Khymeia® VRRS systems (VR) and one group performed the protocol delivered as per normal clinical practice (C). Both groups performed 50-minute protocol 3 days a week for 4 consecutive weeks.
The rehabilitation protocol with virtual reality was carried out by means of semi-immersive (VRRS Handbox) and immersive (Head Mounted Display VRRS device) virtual reality. Motor and cognitive assessments were performed before and after rehabilitation.
Statistically significant improvements and clinical relevance emerged between pre- and post-treatment in the Motricity Index, particularly in the pinch grip, elbow flexion and total score subcategories, Trail Making Test and Thumb Location Test. High satisfaction regarding VR treatment was recorded according to CSQ 8.

AREA TEMATICA

NEUROGENETICA

P166. Archiving of biological materials as the starting point for clinical and research activities: the role of biobanks in advancing neuroscience research

Francesco Colaci1*, Sara Mechregui1*, Raffaele Lodi1,2

1 Neuroscience Biobank of Bologna (BNB), IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy
2 Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy.

*Authors equally contributed to this abstract.

Preservation of biological samples has been transitioning from rudimentary private collections to sophisticated, well-organized biorepositories that serve as the cornerstone for scientific investigations, playing a pivotal role in advancing neuroscience research, particularly in the context of rare neurological disorders. Biobanks gather a diverse array of biological samples, encompassing tissues, biofluids, and genetic materials. Equally important is the commitment to safeguarding the human and legal rights of the participants contributing biomaterials, achieved through a standardized protocol based on data acquisition, pseudonymization, certified technical validation procedures, transparent sharing of biological samples and anonymized clinical and research data. In 2022 we established the Neuroscience Biobank of Bologna (BNB), a research hub with the aim of processing, storing, and distributing biological samples collected from patients diagnosed with neurogenetic, neuromuscular, and neurodegenerative disorders, and associated omics and imaging data. Thus, the core mission of BNB is to facilitate comprehensive research studies, spanning basic, translational, and clinical applications towards the identification of novel biomarkers to optimize diagnosis accuracy. These studies hold the promise of unravelling pathogenetic mechanisms and advancing personalized medical approaches. In 2023 BNB started a partnership with Biobanking and BioMolecular Resources Infrastructure (BBMRI), an EU-wide biobank network developed by the European Commission. Taking part in biobanking effort increases the awareness of European scientific citizenship, highlighting the essential role of biobanks in the quest for enhanced health and improved quality of life.

P171. ANTI-NF155, CNTN1, CASPR1 ANTIBODIES: OPTIMIZATION AND COMPARISON OF LABORATORYMETHODS AND CORRELATION WITH CLINICAL PHENOTYPE

Mobilia E.M.1#, Lechiara A.1#, Pesce G.1,2, Bozzano F.M.1, Baroncelli E.3, Franciotta D.4, Benedetti L.3

1 Autoimmunity Laboratory, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
2 Department of internal Medicine and Specialties (DiMI), University of Genoa, Genoa, Italy.
3 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
4 Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy.

# Co-authors

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disease of the peripheral nervous system. The recent discovery of autoantibodies against paranodal proteins, such as neurofascin-155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1), allowed to define a subgroup of patients with peculiar phenotypes, variably characterized by aggressive onset, failure to respond to intravenous immunoglobulins and tremor of possible cerebellar origin. Current guidelines recommend testing for paranodal antibodies serum samples of patients with CIDP resistant to standard therapies and of those with acute-onset GBS/CIDP.

Methods and results: 69 serum samples from patients with clinical suspect of CIDP (24 F, 45 M; mean age 61 yrs) were tested for anti-NF155, -CNTN1, and -CASPR1 (only 25 samples) IgG with in-house ELISAs (positives: NF155, 2; CNTN1, 4; CASPR1, 7), and with immunofluorescence commercial RUO fixed cell-based-assay (CBA, Euroimmun) (positives: CNTN1, 3; CASPR1, 2). The overall between-test agreement was 76.7 %.

Conclusion: Our preliminary data highlight some degree of analytical discordance between the in-house ELISAs and the commercial RUO CBA. The latter assay displays the antigensin their native conformation, thus suggesting a better specificity. However, assay standardization is lacking, and current guidelines recommend that at least two tests, among ELISA, CBA and rodent sciatic nerve-based assays, should be positive to diagnose paranodal antibody-associated CIDP.

P1770. Complicanze neurologiche da inibitori dei checkpoint immunitari: l’esperienza di un singolo centro

J. Rossi1,2, E. Canali2, L. Codeluppi2, F. Cavallieri2, C. Pinto3, M. Banzi3, F. Valzania2, A. Pisanello2

1 Programma di Dottorato in Medicina Clinica e Sperimentale, Università di Modena e Reggio Emilia, Modena
2 S.C. di Neurologia, Dipartimento Neuromotorio e Riabilitativo, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia
3 S.C. di Oncologia Medica, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia

Introduzione
Gli inibitori dei checkpoint immunitari (ICPI) sono anticorpi monoclonali che agiscono sul sistema immunitario del paziente, modulando l’interazione tra la cellula presentante l’antigene (APC) e i linfociti T. Nonostante l’elevata efficacia, la terapia con ICPI è associata a un ampio spettro di eventi avversi immuno-correlati (irAEs). La miastenia gravis (MG), la miosite, la sindrome di Guillain-Barré (GBS), l’encefalite e la meningite asettica sono i più frequenti irAEs neurologici.

Materiali e metodi
Presentiamo i dati clinici di 7 pazienti afferiti alla Struttura Operativa Complessa di Neurologia dell’IRCCS di Reggio Emilia per complicanze neurologiche secondarie al trattamento con ICPI.

Risultati
Sono stati osservati cinque casi di miastenia gravis, uno di meningite asettica e uno di miosite isolata. In tutti i pazienti gli ICPI sono stati sospesi ed è stata intrapresa una terapia con corticosteroidi. I casi di sindrome miastenica sono stati trattati con immunoglobuline endovena e una paziente è stata sottoposta a plasmaferesi e terapia con metotrexate. Tre pazienti sono deceduti a causa della complicanza neurologica.

Conclusioni
La nostra casistica conferma l’alto rischio di prognosi infausta associato agli irAES. I ICPI attualmente trovano spesso indicazione anche negli stadi iniziali della patologia neoplastica, quando gli irAES potrebbero costituire la principale causa di esito sfavorevole. Risulta quindi fondamentale una caratterizzazione fenotipica sempre più dettagliata di queste entità cliniche emergenti.

AREA TEMATICA

NEUROIMAGING

P184. PySynthMRI: an open-source cross-platform software for generating synthetic radiological images

Luca Perettia,b, Graziella Donatellib,c, Matteo Cencinid, Paolo Cecchib,e, Guido Buonincontria, Mirco Cosottinie,b, Michela Tosettia,b, Mauro Costaglia,f

a) Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris, Pisa, Italy
b) Imago 7 Research Foundation, Pisa, Italy
c) Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
d) Italian National Institute of Nuclear Physics (INFN), Section of Pisa, Pisa, Italy
e) Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
f) Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI), University of Genova, Italy

MRI exams consist of several different acquisition sequences: each sequence duration is in the order of several minutes, and each sequence is designed to achieve only one specific tissue contrast. As a consequence, a complete MRI exam involves long acquisition times that can be challenging for children and uncollaborative patients. A new approach, namely Synthetic MR Imaging has recently been proposed, to generate diverse contrast-weighted MR images from a limited set of acquired images, via post-processing, thus reducing scan times. Commercial products that implement synthetic MRI rely on vendor-specific acquisitions and do not include the possibility of using custom multiparametric imaging techniques. We introduce PySynthMRI, an open-source tool with a user-friendly interface that uses a set of input images (for example, but not necessarily: maps of proton density, T1 and T2) to generate synthetic images with diverse radiological contrasts by varying representative parameters of the desired target sequence, including echo time, repetition time and inversion time(s). PySynthMRI is written in Python 3.6, and it can be executed under Linux, Windows, or MacOS as a python script or an executable. The tool is free and open-source and is developed taking into consideration the possibility of software customization by the end user. Synthetic images can be exported in DICOM or NiFTI format. The distribution provides a set of default synthetic contrasts for neuroimaging applications, including T1w gradient echo, T2w spin echo, T2-FLAIR and Double Inversion Recovery. PySynthMRI is available under free license at https://github.com/FiRMLAB-Pisa/pySynthMRI.git.

P192. Mentalizing Neural Pattern During The Edinburgh Social Cognition fMRI task

Sara Isernia1, Alice Pirastru1,2, Federica Rossetto1, Diego Michael Cacciatore1, Valeria Blasi1, Francesca Baglio1

1 IRCCS Fondazione Don Carlo Gnocchi Onlus, Milan, Italy.
2 Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy.

We aimed to deepen social brain mechanisms during naturalistic mentalizing by adapting and evaluating the stimuli of the Italian version of the Edinburgh Social Cognition test (ESCoT) in a functional Magnetic Resonance Imaging (fMRI) task, which includes animations of everyday life interactions. Forty-two healthy adults (21 males) were administered the fMRI adaptation of ESCoT in a 3T Siemens Prisma scanner. The task was composed of two conditions, Theory of Mind (ToM) versus physical, including ten silent movies each. In the ToM condition, both implicit (movie viewing) and explicit (silent and two-choice answers) mentalizing reasoning neural correlates were stimulated. SPM 12 was used for fMRI data preprocessing. First-level analyses included mentalizing (implicit/explicit) vs physical elements reasoning contrasts. At the group-level, a one-sample t-test for each contrast was performed based on a theory-driven approach, and a statistical threshold of pFWE < 0.05 was adopted. Implicit ToM reasoning evoked neural activations in the bilateral temporoparietal junction (TPJ), superior temporal gyrus (STS), and the left frontal inferior orbital cortex. Explicit ToM reasoning yielded wider neural activations including in addition the bilateral precuneus, the left temporal pole, and the insula. A differential neural pattern for affective and cognitive ToM was also observed, with frontal inferior areas and the STS selectively involved in the affective ToM, whereas the TPJ elicited cognitive ToM. This study contributes to broadening knowledge of human reasoning on mental states during naturalistic social interactions. Future works may employ the task to investigate ToM network reorganization and plasticity in neurological conditions.

P1950. A multicentric, harmonized approach to Quantitative Susceptibility Mapping in mice brain.

Edoardo Micotti 1, Marta Lancione2, Domenico Aquino3, Federica Mazzi3, Lorenzo Carnevale4, Carlo Cavaliere5, Giuseppe Lembo4,6, Marina Grisoli3, Maria Grazia Bruzzone3, Michela Tosetti2, Gianluigi Forloni1

1 Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
2 Laboratory of Medical Physics and Magnetic Resonance, IRCCS Stella Maris Foundation, Pisa, Italy
3 Neuroradiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milan, Italy
4 Unit of Neuro-Cardiovascular Pathophysiology, I.R.C.C.S. Neuromed, Pozzilli, Italy
5 IRCCS Synlab SDN, Naples, Italy.
6 Department of Molecular Medicine, Sapienza University of Rome

Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. Despite its potential, QSM has been so far applied in a few preclinical single-center studies. However, the assessment of the reproducibility is crucial to establish susceptibility as a quantitative biomarker in both human and animal studies.
The goal of this project, promoted by the Italian IRCCS Network of Neuroscience and Neuro-rehabilitation (RIN), is the harmonization of acquisition and image analysis between human and animal studies. This process led to a multicentric, QSM protocol to be tested in animal models. Two groups of adult female WT mice (n=8), age matched (5 months), underwent the same QSM protocols in two different laboratories. MRI parameters have been previously standardized (a 3D Gradient Echo sequence, with isotropic resolution of 0.15 mm and 8 echo times) in accordance with literature and clinical protocols. Data have been then analysed adapting a pipeline already established in the human work packages of the project [1]. These preliminary results show a good accordance of absolute susceptibility values between the two laboratories, mostly in white matter tracts. The next steps will be to improve the quality of acquired data and apply the QSM protocol to a longitudinal, multicentric, harmonized study of a relevant mouse model of neurodegeneration.

AREA TEMATICA

MALATTIE DEL MOTONEURONE

P202. MAY NIV IMPROVE SWALLOWING IN AMYOTROPHIC LATERAL SCLEROSIS PATIENTS?

Silvia Grilli1, Rachele Piras1, Antonino Iannello1, Sara del Bue1, Valentina Rivolta1, Christian Lunetta1

1 Istituti Clinici Scientifici Maugeri IRCCS, Department of Neurorehabilitation of the Milano Institute, Milan, Italy

Non-invasive ventilation plays a key role in improving the quality of life and prognosis of Amyotrophic Lateral Sclerosis (ALS), the most common adult onset motor neuron degenerative disease patients. Although numerous studies have primarily investigated the indications and effects of nighttime ventilation, only a few have examined the efficacy of pressure and volume settings for effective daytime ventilation, and specifically during specific activity daily living.

As the disease progresses, it necessitates an extension of the hours of ventilation, and patients often require a nasal mask to facilitate speaking and eating during daytime ventilation. Our study delves into the crucial aspect of meal management and calorie intake for ALS patients during daytime ventilation. Recent literature, has established a connection between weight loss, malnutrition, sarcopenia, and a poorer prognosis.

Furthermore, we aim to assess how non-invasive ventilation during meals can enhance meal management in terms of food intake, time efficiency, and patient-reported outcomes such as fatigue, perceived dyspnea, and overall quality of life. The workflow involves clinical assessment using specific scales, logopedic evaluations during meals, and intervention from respiratory physiotherapists. All patients were assessed both before and after commencing non-invasive ventilation with a nasal mask during meals.

In our experience of 10 enrolled patients, the proper management of non-invasive ventilation has led to improvements in food intake, reduced dyspnea and fatigue, and the safe extension of oral feeding, ultimately enhancing the nutritional status and quality of life of ALS patients.

AREA TEMATICA

SCLEROSI MULTIPLA E DISORDINI NEUROIMMUNOLOGICI

P211. Identification of B cell-related gene variants as predictive biomarkers for personalized medicine in myasthenia gravis

Paola Cavalcante,1 Erika Salvi,2 Gregorio Spagni,3 Fiammetta Vanoli,1 Rita Frangiamore,1 Raffaella Brugnoni,1 Federica Bortone,1 Marta Ballardini,1 Maria Cristina Tarasco,1,4 Nicola Iacomino,1 Stefania Magri,5 Valentina Damato,3,6 Carlo Antozzi,1 Maria Foti,7 Amelia Evoli,3 Renato Mantegazza1

1 Neurology 4 – Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
2 Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
3 Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy
4 Ph.D. program in Neuroscience, University of Milano-Bicocca, Monza, Italy
5 Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
6 Department of Neurosciences, Drugs and Child Health, University of Florence, Florence, Italy
7 Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

Myasthenia Gravis (MG) is a B cell-mediated autoimmune disease affecting neuromuscular junction. Current treatments for MG allow to control symptoms, but most patients do not achieve complete stable remission, requiring lifelong immunosuppressive (IS) therapy, and approximately 10-15% of them is refractory to IS drugs. Inter-individual variability in drug efficacy poses a challenge to clinicians, highlighting the need of personalized medicine (PM) strategies to improve therapeutic success. We assessed the association between variants in genes modulating B cell function (i.e. activation, differentiation, survival) and treatment response in MG patients. A targeted NGS panel was designed to sequence 70 B cell-related genes, including all the exons, ± 50 bp flanking sequences from intron-exon boundary, 5’ and 3′ UTRs. Panel sequencing was performed in 88 patients stratified as responder (R, n=44) and non-responder (NR, n=44) to IS drugs. Validation of selected variants was performed in additional 83 patients (48 R, 35 NR) by allelic discrimination. We revealed missense and 5’UTR variants significantly associated with refractoriness to IS drugs in the following genes: i) CR1, encoding a complement system regulator; ii) LILRB2, encoding an Ig-like immunoinhibitory receptor; and iii) CREB1, encoding an inflammatory mediator. Our findings could contribute to the adoption of genetic biomarker-based PM approaches in MG practice to predict unresponsiveness to IS drugs and early direct NR patients towards other therapeutic options, such as treatment with the new biological drugs. Work supported by: Italian Ministry of Health (RRC, RF-2016-02364384) and Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), Project ERAPERMED2022-258, GA 779282.

P212. Inaugural undertaking aimed at evaluating the viability of PET imaging for assessing myelination in the spinal cord of individuals diagnosed with multiple sclerosis.

A. Cirone2 , M. Pardini1,2, L. Roccatagliata1,2, G. Novi1 , C. Campi 1,2, A. Donniaquio1,2 , L. Sofia1,2, A. Laroni1,2, A. Murialdo1,2, G. Ribizzi1,2, M. Bauckneht1,2, S. Garbarino2 , G. Sambuceti1,2 , L. Argenti1,2 , M. I. Donegani1,2 , M. Piana1,2 , A. Chincarini3 , A. Uccelli1,2 , S. Morbelli1,2

1 University of Genoa, Genoa, Italy
2 IRCCS Ospedale Policlinico San Martino, Genoa, Italy
3 Genoa Division, National Institute for Nuclear Physics, Genoa, Italy

PET imaging using β-amyloid ligands (amy-PET) is emerging as a molecular imaging technique with
the aim of quantitatively measuring changes in myelin content in multiple sclerosis (MS). Initial
evidence supports the capacity of amy-PET to assess demyelination and remyelination in cerebral
white matter (WM). However, there is still a lack of data regarding the ability of these tracers to
capture myelin dynamics in the spinal cord. In a project funded by the Italian Ministry of Health, 24
patients with either relapsing-remitting (RR) or primary progressive (PP) MS were recruited. All
patients underwent amy-PET imaging with [18F]Florbetaben, which included standard brain scans
and body scans to assess amy-PET signals in the spinal cord’s white matter. Following the
segmentation of the spinal canal (with individual vertebrae considered separately from C2 to L5),
standardized uptake values were measured to estimate metabolic activity. These measurements
were taken in the cervical, dorsal, and lumbar spine and then normalized to the corresponding
values in either the liver or aortic blood-pool (SUVrL and SUVrB, respectively). Furthermore,
correlations were identified between the normalized uptake and specific clinical indicators. Our
approach facilitated the evaluation of WM amy-PET signal in the spinal cord, offering a potential
new perspective on the pathophysiology of demyelination and remyelination in multiple sclerosis.

Inaugural undertaking aimed at evaluating the viability of PET imaging for assessing myelination in the spinal cord of individuals diagnosed w ith multiple sclerosis

Authors: A. Cirone2, M. Pardini1,2, L. Roccatagliata1,2, G. Novi1, C. Campi1,2, A. Donniaquio1,2, L. Sofia1,2, A. Laroni1,2, A. Murialdo1,2, G. Ribizzi1,2, M. Bauckneht1,2, S. Garbarino2, G. Sambuceti1,2, L. Argenti1,2, M. I. Donegani1,2, M. Piana1,2, A. Chincarini3, A. Uccelli1,2, S. Morbelli1,2.

Affiliations:
1 University of Genoa, Genoa, Italy
2 IRCCS Ospedale Policlinico San Martino, Genoa, Italy
3 Genoa Division, National Institute for Nuclear Physics, Genoa, Italy

Abstract:
PET imaging using β amyloid ligands (amy PET) is emerging as a molecular imaging technique with the aim of quantitatively measuring changes in myelin content in multiple sclerosis (MS). Initial evidence supports the capacity of amy PET to assess demyelination and remyelination in cerebral white matter (WM). However, there is still a lack of data regarding the ability of these tracers to capture myelin dynamics in the spinal cord. In a project funded by the Italian Min istry of Health, 24 patients with either relapsing remitting (RR) or primary progressive (PP) MS were recruited. All patients underwent amy PET imaging with [18F]Florbetaben, which included standard brain scans and body scans to assess amy PET signals in t he spinal cord’s white matter. Following the segmentation of the spinal canal (with individual vertebrae considered separately from C2 to L5), standardized uptake values were measured to estimate metabolic activity. These measurements were taken in the cer vical, dorsal, and lumbar spine and then normalized to the corresponding values in either the liver or aortic blood pool (SUVrL and SUVrB, respectively). Furthermore, correlations were identified between the normalized uptake and specific clinical indicato rs. Our approach facilitated the evaluation of WM amy PET signal in the spinal cord , offering a potential new perspective on the pathophysiology of demyelination and remyelination in multiple sclerosis.

Acknowledgements:
The authors acknowledge financial contribution from the Italian Ministry of Health, with the project NeuroArtP3 (NET 2018 12366666)