M Gastaldi1, S Mariotto2, M P Giannoccaro3,4, R Iorio5,6, M Zoccarato7,8, M Nosadini8,9, L Benedetti10, S Casagrande11,12, M Di Filippo13, M Valeriani14, S Ricci15, S Bova16, C Arbasino17, M Mauri18, M Versino18, F Vigevano14, L Papetti14, M Romoli13,19, C Lapucci10, F Massa10, S Sartori8,9, L Zuliani8,20, A Barilaro12, P De Gaspari8, G Spagni6, A Evoli5,6, R Liguori3,4, S Ferrari2, E Marchioni21, B Giometto22, L Massacesi11,12, D Franciotta1. 1. Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. 2. Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 3. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 4. UOC Clinica Neurologica, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. 5. Istituto di Neurologia, Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS, Rome, Italy. 6. Universita' Cattolica del Sacro Cuore, Rome, Italy. 7. Ospedale S. Antonio, AULSS Euganea, Padua, Italy. 8. Neuroimmunology Group, Paediatric Research Institute "Città della Speranza", Padua, Italy. 9. Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy. 10. IRCCS Ospedale Policlinico S. Martino, Genoa, Italy. 11. Neurosciences Department, Florence University, Italy. 12. Careggi University Hospital, Florence, Italy. 13. Neurology Clinic, S. Maria della Misericordia Hospital, Perugia University, Perugia, Italy. 14. Neurology Unit, Bambino Gesù Children Hospital, Rome, Italy. 15. Ospedale 'Città-di-Castello-e-Branca', Italy. 16. Pediatric Neurology Unit, ASST Fatebenefratelli Sacco, Children Hospital Vittore Buzzi, Milan, Italy. 17. Ospedale Civile, Voghera, Italy. 18. Neurology and Stroke Unit, Insubria University, Varese, Italy. 19. Neurology Unit, Rimini "Infermi" Hospital - AUSL Romagna, Rimini, Italy. 20. Neurology Department, Ospedale S. Bortolo, Vicenza, Italy. 21. Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy. 22. APSS Ospedale S. Chiara, Trento, Italy.
Abstract
BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.
BACKGROUND AND PURPOSE:Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AEpatients were treated earlier than Ab-negative-AEpatients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AEpatients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AEpatients risk worse responses due to delayed and less aggressive treatments.