Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France

Hébert, J.; Riche, Benjamin; Vogrig, Alberto; Muñiz‐Castrillo, Sergio; Joubert, Bastien; Picard, Géraldine; Rogemond, Véronique; Psimaras, Dimitri; Alentorn, Agustí; Berzero, Giulia; Desestret, Virginie; Rabilloud, Muriel; Honnorat, Jérôme

doi:10.1212/nxi.0000000000000883

Cited by 98 publications

(74 citation statements)

References 25 publications

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“…In our cohort, the sex ratio was close to equal, with NMDAR encephalitis occurring slightly more frequently in men than women. Similar sex ratio was observed in a cohort of Chinese AE patients (12), although, published data claims that anti-NMDAR encephalitis affects predominantly young women (median age, 21 years) (3,22). Dalmau et al (3) reported male predominance in LGI1, GABABR and Caspr2 encephalitis, which was also observed in our cohort, although, the median age of our AE patients were 45-50 years compared to median values of 60-65 years in previous publications (3,23).…”

Section: Discussionsupporting

confidence: 76%

Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

et al. 2021

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Background: In our previous single-center study of autoimmune encephalitis (AE) related autoantibody test results we found positivity in 60 patients out of 1,034 with suspected AE from 2012 through 2018 as part of a Hungarian nationwide program. In our current multicenter retrospective study, we analyzed the clinical characteristics and outcome of AE patients with positive neuronal cell surface autoantibody test results.Methods: A standard online questionnaire was used to collect demographic and clinical characteristics, laboratory and imaging data, therapy and prognosis of 30 definitive AE patients in four major clinical centers of the region.Results: In our study, 19 patients were positive for anti-NMDAR (63%), 6 patients (20%) for anti-LGI1, 3 patients for anti-GABABR (10%) and 3 patients for anti-Caspr2 (10%) autoantibodies. Most common prodromal symptoms were fever or flu-like symptoms (10/30, 33%). Main clinical features included psychiatric symptoms (83%), epileptic seizures (73%) and memory loss (50%). 19 patients (63%) presented with signs of central nervous system (CNS) inflammation, which occurred more frequently in elder individuals (p = 0.024), although no significant differences were observed in sex, tumor association, time to diagnosis, prognosis and immunotherapy compared to AE patients without CNS inflammatory markers. Anti-NMDAR encephalitis patients were in more severe condition at the disease onset (p = 0.028), although no significant correlation between mRS score, age, sex and immunotherapy was found. 27% of patients (n = 8) with associated tumors had worse outcome (p = 0.045) than patients without tumor. In most cases, immunotherapy led to clinical improvement of AE patients (80%) who achieved a good outcome (mRS ≤ 2; median follow-up 33 months).Conclusion: Our study confirms previous publications describing characteristics of AE patients, however, differences were observed in anti-NMDAR encephalitis that showed no association with ovarian teratoma and occurred more frequently among young males. One-third of AE patients lacked signs of inflammation in both CSF and brain MRI, which emphasizes the importance of clinical symptoms and autoantibody testing in diagnostic workflow for early introduction of immunotherapy, which can lead to favorable outcome in AE patients.

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Section: Discussionsupporting

confidence: 76%

Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

et al. 2021

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“…A more useful parameter in clinical practice is the positive predictive value (PPV), which is the ratio between true positives and total positive results obtained by testing a given population, and is highly dependent on the frequency of the disease of interest in the population tested and the test ordering practices (106). This is particularly relevant for rare disorders like autoimmune neurologic disorders, for which the reported overall incidence and prevalence range between 3.5 and 9/million person-years and 4-6.5/100.000 persons, respectively (107)(108)(109). When similar rare disorders are faced, caution is advised in clinical practice as the risk of false positive results is not negligible if the test is performed indiscriminately, despite very high specificity and sensitivity (110).…”

Section: Positive Predictive Value False Positives and "Phenotype Creep"mentioning

confidence: 99%

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Sechi

Flanagan

2021

Front. Neurol.

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Antibody-mediated disorders of the central nervous system (CNS) are increasingly recognized as neurologic disorders that can be severe and even life-threatening but with the potential for reversibility with appropriate treatment. The expanding spectrum of newly identified autoantibodies targeting glial or neuronal (neural) antigens and associated clinical syndromes (ranging from autoimmune encephalitis to CNS demyelination) has increased diagnostic precision, and allowed critical reinterpretation of non-specific neurological syndromes historically associated with systemic disorders (e.g., Hashimoto encephalopathy). The intracellular vs. cell-surface or synaptic location of the different neural autoantibody targets often helps to predict the clinical characteristics, potential cancer association, and treatment response of the associated syndromes. In particular, autoantibodies targeting intracellular antigens (traditionally termed onconeural autoantibodies) are often associated with cancers, rarely respond well to immunosuppression and have a poor outcome, although exceptions exist. Detection of neural autoantibodies with accurate laboratory assays in patients with compatible clinical-MRI phenotypes allows a definite diagnosis of antibody-mediated CNS disorders, with important therapeutic and prognostic implications. Antibody-mediated CNS disorders are rare, and reliable autoantibody identification is highly dependent on the technique used for detection and pre-test probability. As a consequence, indiscriminate neural autoantibody testing among patients with more common neurologic disorders (e.g., epilepsy, dementia) will necessarily increase the risk of false positivity, so that recognition of high-risk clinical-MRI phenotypes is crucial. A number of emerging clinical settings have recently been recognized to favor development of CNS autoimmunity. These include antibody-mediated CNS disorders following herpes simplex virus encephalitis or occurring in a post-transplant setting, and neurological autoimmunity triggered by TNFα inhibitors or immune checkpoint inhibitors for cancer treatment. Awareness of the range of clinical and radiological manifestations associated with different neural autoantibodies, and the specific settings where autoimmune CNS disorders may occur is crucial to allow rapid diagnosis and early initiation of treatment.

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“…Yet, stated incidence varies from 1.6 to 8.9 per million person-years, suggesting that underdiagnosis and underreporting are still relevant issues. 3,4 It is likely that the expanding use of immune checkpoint inhibitors (ICIs) in oncologic practice will lead to an increased frequency of similar syndromes. 5,6 In 2004, a set of recommended diagnostic criteria for PNS were defined by a panel of international experts and became the standard for clinical and research purposes.…”

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confidence: 99%

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

Graus

Vogrig

Muñiz‐Castrillo

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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436

378

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ObjectiveThe contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.MethodsA panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project.ResultsThe panel proposed to substitute “classical syndromes” with the term “high-risk phenotypes” for cancer and introduce the concept of “intermediate-risk phenotypes.” The term “onconeural antibody” was replaced by “high risk” (>70% associated with cancer) and “intermediate risk” (30%–70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.ConclusionsThe proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

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Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France

Cited by 98 publications

References 25 publications

Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

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