Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study.

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 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, 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. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. FUNDING: The Instituto de Salud Carlos III and the European Union.

Optic neuritis in pregnancy after Tdap vaccination: Report of two cases.

Two pregnant women developed one-eye blurring vision within three weeks after Tdap vaccination. Neurophtalmologic and MR examination confirmed an unilateral optic neuritis without evidence of underlying disease. Both patients had a full recovery, one after intravenous metilprednisolone. This is the first report of optic neuritis related with Tdap vaccination in pregnancy.

Timectomía en miastenia grave timomatosa y no timomatosa: análisis de una cohorte de 46 pacientes / Thymectomy in thymomatous and non-thymomatous myasthenia gravis: analysis of a cohort of 46 patients

INTRODUCCIÓN: En la actualidad, los factores predictores de remisión de la enfermedad en la miastenia grave tras una timectomía no están claramente establecidos. OBJETIVO: Analizar la evolución clínica de los pacientes tras esta intervención y abordar los posibles determinantes pronósticos. PACIENTES Y MÉTODOS: Se analizaron retrospectivamente los registros de pacientes con miastenia grave timectomizados en nuestro centro entre 2006 y 2016. Se utilizó la escala Miasthenya Gravis Foundation of America-Post Intervention Status agrupando las categorías «remisión completa estable», «remisión farmacológica», «manifestaciones mínimas» y «mejoría» como «buen resultado clínico», y las categorías «sin cambios», «empeoramiento», «exacerbación» y «muerte», como «mal resultado clínico». RESULTADOS: Se analizaron 46 timectomías de pacientes con miastenia grave, un 71,7% mujeres. La mediana de edad era de 37 años y el 10,9% asociaba enfermedades autoinmunes. El timoma (23,9%) fue más frecuentes en los varones (54,5% frente a 18,8%) y a mayor edad (53 ± 20 frente a 33 ± 24 años). Un año después de la timectomía, el 28,2% se encontraba en el grupo de mal resultado clínico, y un 54,3%, en el de buen resultado clínico. En el análisis univariante, el timoma se asoció a peor resultado clínico al año de la intervención. Tras diez años de seguimiento, 32 pacientes (78%) alcanzaron un buen resultado clínico, un 9,8% en remisión completa estable, y el timoma no se correlacionó como factor de mal pronóstico. CONCLUSIÓN: La timectomía se considera un tratamiento efectivo, pero sin beneficio inmediato. La presencia de timoma podría determinar una respuesta clínica inicial peor tras la realización de una timectomía en pacientes con miastenia grave

INTRODUCTION: Factors predicting remission after thymectomy for myasthenia gravis are not well known. AIM: To analyze the clinical evolution of the patients after this intervention and discuss about predictors of response. PATIENTS AND METHODS: We retrospectively reviewed all clinical data of thymectomies in myasthenia gravis patients performed at our hospital between 2006 from 2016. Using the MGFA-PIS classification, «complete stable remission», «pharmacologic remission», «minimal manifestations» and «improved» were defined as «good clinical outcome», and «unchanged», «worse», «exacerbation» or «died», as «poor clinical outcome». RESULTS: In 46 consecutive thymectomies for myasthenia gravis, women comprised 71.7%. Median age was 37 years and 10.9% had concomitant autoimmune disorders associated. Thymoma (23.96%) was more frequent in older patients (53 ± 20 vs 33 ± 24 years) and men (54.5% vs 18.8%). A year after thymectomy, 28.2% of patients were in poor clinical outcome group and 54.3% had good clinical outcome. On univariate analysis, thymomatous myasthenia was associated with poor clinical outcome a year after surgical intervention. After ten years of follow-up, 9.8% reached complete stable remission, a total of 32 patients (78%) had a favourable outcome and thymoma was not correlated. CONCLUSION. Thymectomy is considered an effective treatment for myasthenia gravis but the benefit is not immediate. The presence of thymoma may determine a worse initial clinical response following thymectomy in patients with myasthenia gravis

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia: a double-edged sword.

JOURNAL/nrgr/04.03/01300535-202508000-00029/figure1/v/2024-09-30T120553Z/r/image-tiff Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system, including retinal ganglion cell axonal growth through the injured optic nerve. Still, it is unknown whether olfactory ensheathing glia also have neuroprotective properties. Olfactory ensheathing glia express brain-derived neurotrophic factor, one of the best neuroprotectants for axotomized retinal ganglion cells. Therefore, we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush. Olfactory ensheathing glia cells from an established rat immortalized clonal cell line, TEG3, were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments. Anatomical and gene expression analyses were performed. Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex class II molecules. Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days, forming an epimembrane. In axotomized retinas, only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days. In these retinas, microglial anatomical activation was higher than after optic nerve crush alone. In intact retinas, both transplants activated microglial cells and caused retinal ganglion cell death at 21 days, a loss that was higher after allotransplantation, triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression. However, neuroprotection of axotomized retinal ganglion cells did not improve with these treatments. The different neuroprotective properties, different toxic effects, and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.