Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study

M Gastaldi, S Mariotto, M P Giannoccaro, R Iorio, M Zoccarato, M Nosadini, L Benedetti, S Casagrande, M Di Filippo, M Valeriani, S Ricci, S Bova, C Arbasino, M Mauri, M Versino, F Vigevano, L Papetti, M Romoli, C Lapucci, F MassaS Sartori, L Zuliani, A Barilaro, P De Gaspari, G Spagni, A Evoli, R Liguori, S Ferrari, E Marchioni, B Giometto, L Massacesi, D Franciotta

Research output: Contribution to journalArticle

Abstract

BACKGROUND: 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. We studied AE-DC impact on patients' management, focusing on the subgroup of Ab-negative-AE.

METHODS: 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 define final categories. Patients were classified as Ab-positive-AE [NMDAR-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%). One-hundred-eighteen patients fulfilled AE-DC, 81(68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, 9), 37(31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive- vs 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 associated with poor response (p=0.022; OR,1.02; CI,1.00-1.04).

CONCLUSIONS: In-house diagnostics improved Ab detection, allowing better patients' 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 share similar oncologic profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
Publication statusE-pub ahead of print - Dec 8 2019

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Limbic Encephalitis
Multicenter Studies
Retrospective Studies
Phenotype
Encephalitis
Hashimoto's encephalitis
Antibodies
Therapeutics
Nervous System Diseases
Neoplasms
Immunohistochemistry

Cite this

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis : a multicenter retrospective study. / Gastaldi, M; Mariotto, S; Giannoccaro, M P; Iorio, R; Zoccarato, M; Nosadini, M; Benedetti, L; Casagrande, S; Di Filippo, M; Valeriani, M; Ricci, S; Bova, S; Arbasino, C; Mauri, M; Versino, M; Vigevano, F; Papetti, L; Romoli, M; Lapucci, C; Massa, F; Sartori, S; Zuliani, L; Barilaro, A; De Gaspari, P; Spagni, G; Evoli, A; Liguori, R; Ferrari, S; Marchioni, E; Giometto, B; Massacesi, L; Franciotta, D.

In: European Journal of Neurology, 08.12.2019.

Research output: Contribution to journalArticle

Gastaldi, M, Mariotto, S, Giannoccaro, MP, Iorio, R, Zoccarato, M, Nosadini, M, Benedetti, L, Casagrande, S, Di Filippo, M, Valeriani, M, Ricci, S, Bova, S, Arbasino, C, Mauri, M, Versino, M, Vigevano, F, Papetti, L, Romoli, M, Lapucci, C, Massa, F, Sartori, S, Zuliani, L, Barilaro, A, De Gaspari, P, Spagni, G, Evoli, A, Liguori, R, Ferrari, S, Marchioni, E, Giometto, B, Massacesi, L & Franciotta, D 2019, 'Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study', European Journal of Neurology. https://doi.org/10.1111/ene.14139
Gastaldi, M ; Mariotto, S ; Giannoccaro, M P ; Iorio, R ; Zoccarato, M ; Nosadini, M ; Benedetti, L ; Casagrande, S ; Di Filippo, M ; Valeriani, M ; Ricci, S ; Bova, S ; Arbasino, C ; Mauri, M ; Versino, M ; Vigevano, F ; Papetti, L ; Romoli, M ; Lapucci, C ; Massa, F ; Sartori, S ; Zuliani, L ; Barilaro, A ; De Gaspari, P ; Spagni, G ; Evoli, A ; Liguori, R ; Ferrari, S ; Marchioni, E ; Giometto, B ; Massacesi, L ; Franciotta, D. / Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis : a multicenter retrospective study. In: European Journal of Neurology. 2019.
@article{3bb81106cf574e8c9d2e6d4416e7fd1a,
title = "Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study",
abstract = "BACKGROUND: 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. We studied AE-DC impact on patients' management, focusing on the subgroup of Ab-negative-AE.METHODS: 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 define final categories. Patients were classified as Ab-positive-AE [NMDAR-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{\%}). One-hundred-eighteen patients fulfilled AE-DC, 81(68.6{\%}) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, 9), 37(31.4{\%}) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive- vs 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 associated with poor response (p=0.022; OR,1.02; CI,1.00-1.04).CONCLUSIONS: In-house diagnostics improved Ab detection, allowing better patients' 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 share similar oncologic profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.",
author = "M Gastaldi and S Mariotto and Giannoccaro, {M P} and R Iorio and M Zoccarato and M Nosadini and L Benedetti and S Casagrande and {Di Filippo}, M and M Valeriani and S Ricci and S Bova and C Arbasino and M Mauri and M Versino and F Vigevano and L Papetti and M Romoli and C Lapucci and F Massa and S Sartori and L Zuliani and A Barilaro and {De Gaspari}, P and G Spagni and A Evoli and R Liguori and S Ferrari and E Marchioni and B Giometto and L Massacesi and D Franciotta",
note = "{\circledC} 2019 EAN.",
year = "2019",
month = "12",
day = "8",
doi = "10.1111/ene.14139",
language = "English",
journal = "European Journal of Neurology",
issn = "1351-5101",
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TY - JOUR

T1 - Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis

T2 - a multicenter retrospective study

AU - Gastaldi, M

AU - Mariotto, S

AU - Giannoccaro, M P

AU - Iorio, R

AU - Zoccarato, M

AU - Nosadini, M

AU - Benedetti, L

AU - Casagrande, S

AU - Di Filippo, M

AU - Valeriani, M

AU - Ricci, S

AU - Bova, S

AU - Arbasino, C

AU - Mauri, M

AU - Versino, M

AU - Vigevano, F

AU - Papetti, L

AU - Romoli, M

AU - Lapucci, C

AU - Massa, F

AU - Sartori, S

AU - Zuliani, L

AU - Barilaro, A

AU - De Gaspari, P

AU - Spagni, G

AU - Evoli, A

AU - Liguori, R

AU - Ferrari, S

AU - Marchioni, E

AU - Giometto, B

AU - Massacesi, L

AU - Franciotta, D

N1 - © 2019 EAN.

PY - 2019/12/8

Y1 - 2019/12/8

N2 - BACKGROUND: 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. We studied AE-DC impact on patients' management, focusing on the subgroup of Ab-negative-AE.METHODS: 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 define final categories. Patients were classified as Ab-positive-AE [NMDAR-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%). One-hundred-eighteen patients fulfilled AE-DC, 81(68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, 9), 37(31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive- vs 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 associated with poor response (p=0.022; OR,1.02; CI,1.00-1.04).CONCLUSIONS: In-house diagnostics improved Ab detection, allowing better patients' 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 share similar oncologic profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

AB - BACKGROUND: 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. We studied AE-DC impact on patients' management, focusing on the subgroup of Ab-negative-AE.METHODS: 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 define final categories. Patients were classified as Ab-positive-AE [NMDAR-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%). One-hundred-eighteen patients fulfilled AE-DC, 81(68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, 9), 37(31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive- vs 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 associated with poor response (p=0.022; OR,1.02; CI,1.00-1.04).CONCLUSIONS: In-house diagnostics improved Ab detection, allowing better patients' 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 share similar oncologic profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

U2 - 10.1111/ene.14139

DO - 10.1111/ene.14139

M3 - Article

C2 - 31814224

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

ER -