Browsing by Author "Fonseca, Elianet"

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    mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis
    (2023) Blanco, Yolanda; Escudero, Domingo; Lleixa, Cinta; Llufriu, Sara; Egri, Natalia; Garcia, Raquel Ruiz; Alba, Mercedes; Aguilar, Esther; Artola, Montse; Aldea Novo, Marta; Alvarez, Silvia; Caballero, Eva; Cabrera-Maqueda, Jose Maria; Fonseca, Elianet; Guasp, Mar; Hernando, Ana; Martinez-Hernandez, Eugenia; Olive-Cirera, Gemma; Lopez-Contreras, Joaquin; Martin-Aguilar, Lorena; Martinez-Martinez, Laura; Rombauts, Alexander; Rodes, Maria; Sabater, Lidia; Sepulveda, Maria; Solana, Elisabeth; Tejada-Illa, Clara; Vidal-Fernandez, Nuria; Vilella, Anna; Fortuny, Claudia; Armangue, Thais; Dalmau, Josep O.; Querol, Luis; Saiz, Albert
    Background and ObjectiveIn people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.MethodsThis was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens.ResultsAmong 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred.DiscussionIn this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable.
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    Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study
    (2023) Fonseca, Elianet; Cabrera-Maqueda, Jose M.; Ruiz-Garcia, Raquel; Naranjo, Laura; Diaz-Pedroche, Carmen; Velasco, Roser; Macias-Gomez, Adria; Milisenda, Jose C.; Munoz-Farjas, Elena; Pascual-Goni, Elba; Perez-Larraya, Jaime Gallego; Saiz, Albert; Dalmau, Josep; Blanco, Yolanda; Graus, Francesc; Martinez-Hernandez, Eugenia
    Background Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival.Methods This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors.Findings From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2 center dot 5, 95% CI 1 center dot 1-6 center dot 0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5 center dot 0, 1 center dot 4-17 center dot 8 and HR 6 center dot 6, 1 center dot 4-31 center dot 0, respectively).Interpretation Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death.
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    Opsoclonus-myoclonus syndrome associated with anti Kelch-like protein-11 antibodies in a young female patient without cancer
    (2021) Fonseca, Elianet; Varas, Rene; Godoy-Santin, Jaime; Valenzuela, Raul; Sandoval, Patricio
    Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder. The pathogenesis is thought to be immune-mediated. In adults, it may be idiopathic or paraneoplastic in origin. However, most cases of paraneoplastic OMS in adults are not associated with well-characterized antibodies, except for a small subgroup who have anti-Ri antibodies. Herein, we provide the first detailed description of a case of OMS associated with a Kelch-like protein-11 antibody, a newly discovered biomarker for paraneoplastic neurological syndromes associated with germ-cell tumors. This was a young female patient in whom no tumor was ever detected and who had an excellent response to rituximab.
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    Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis
    (2024) Alba-Arbalat, Salut; Solana, Elisabeth; Lopez-Soley, Elisabet; Camos-Carreras, Anna; Martinez-Heras, Eloy; Vivo, Francesc; Pulido-Valdeolivas, Irene; Andorra, Magi; Sepulveda, Maria; Cabrera, Jose Maria; Fonseca, Elianet; Calvi, Alberto; Alcubierre, Rafel; Dotti-Boada, Marina; Saiz, Albert; Martinez-Lapiscina, Elena H.; Villoslada, Pablo; Blanco, Yolanda; Sanchez-Dalmau, Bernardo; Llufriu, Sara
    Background We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease.Method We quantified the peripapillary retinal nerve fibre (pRFNL) and ganglion cell-inner plexiform (GCIPL) layers thicknesses of 207 PwMS and performed neuropsychological evaluations. The cohort was divided based on disease duration (<= 5 years or >5 years). We studied associations between changes in OCT and cognition over time, and assessed the risk of cognitive decline of a pRFNL <= 88 mu m or GCIPL <= 77 mu m and its predictive value.Results Changes in pRFNL and GCIPL thickness over 3.2 years were associated with evolution of cognitive scores, in the entire cohort and in patients with more than 5 years of disease (p<0.01). Changes in cognition were related to less use of disease-modifying drugs, but not OCT metrics in PwMS within 5 years of onset. A pRFNL <= 88 mu m was associated with earlier cognitive disability (3.7 vs 9.9 years) and higher risk of cognitive deterioration (HR=1.64, p=0.022). A GCIPL <= 77 mu m was not associated with a higher risk of cognitive decline, but a trend was observed at <= 91.5 mu m in PwMS with longer disease (HR=1.81, p=0.061).Conclusions The progressive retinal thinning is related to cognitive decline, indicating that cognitive dysfunction is a late manifestation of accumulated neuroaxonal damage. Quantifying the pRFNL aids in identifying individuals at risk of cognitive dysfunction.