Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.
Neurol Neuroimmunol Neuroinflamm. 2024-05-01; 11(3):
DOI: 10.1212/nxi.0000000000200229
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1. Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200229. doi:
10.1212/NXI.0000000000200229. Epub 2024 Apr 24.
Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune
Encephalitis With GABA(B)R Antibodies.
Lamblin F(1), Kerstens J(1), Muñiz-Castrillo S(1), Vogrig A(1), Goncalves D(1),
Rogemond V(1), Picard G(1), Villard M(1), Pinto AL(1), Van Coevorden-Hameete
MH(1), De Bruijn MA(1), De Vries JM(1), Schreurs M(1), Tyvaert L(1), Hopes L(1),
Aupy J(1), Marchal C(1), Psimaras D(1), Kremer L(1), Bourg V(1), Antoine JG(1),
Wang A(1), Kahane P(1), Demeret S(1), Ahle G(1), Sempere VP(1), Timestit N(1),
Nourredine M(1), Maureille A(1), Benaiteau M(1), Joubert B(1), Mignot E(1),
Titulaer MJ(1), Honnorat J(1).
Author information:
(1)From the French Reference Center on Paraneoplastic Neurological Syndrome and
Autoimmune Encephalitis (F.L., V.R., G.P., M.V., A.-L.P., M.B., B.J., J.H.),
Hospices Civils de Lyon; Institut MeLiS INSERM U1314/CNRS UMR 5284 (F.L., V.R.,
G.P., M.V., A.-L.P., M.B., B.J., J.H.), Université Claude Bernard Lyon 1;
Department of Neurology (F.L.), University Hospital of La Réunion, Saint-Pierre
(La Réunion), France; Department of Neurology (J.K., M.H.V.C.-H., M.A.D.B.,
J.M.V., M.J.T.), Erasmus Medical Center, Rotterdam, The Netherlands; Stanford
Center for Sleep Sciences and Medicine (S.M.-C., V.P.S., E.M.), Stanford
University, Palo Alto, CA; Clinical Neurology (A.V.), Department of
Neurosciences, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC);
Department of Medicine (DAME) (A.V.), University of Udine Medical School, Italy;
Department of Immunology (D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon,
France; Department of Immunology (M.S.), Laboratory Medical Immunology, Erasmus
Medical Center, Rotterdam, The Netherlands; Department of Neurology (L.T.,
L.H.), University Hospital of Nancy; Department of Clinical Neurosciences (J.A.,
C.M.), University Hospital of Bordeaux, Bordeaux, France; Department of
Neuro-Oncology (D.P.), Pitié Salpêtrière Hospital, AP-HP, Paris; Department of
Neurology (L.K.), University Hospital of Strasbourg; Department of Neurology
(V.B.), Côte d’Azur University, Nice; Department of Neurology (J.-C.G.A.),
University Hospital of Saint-Etienne; Stroke Center Neurology Division (A.W.),
Hopital Foch, Suresnes; University Grenoble Alpes (P.K.), Inserm, U1216, CHU
Grenoble Alpes, Grenoble Institut Neurosciences; Neurological Intensive Care
Unit (S.D.), Pitié-Salpêtrière Hospital, AP-HP, Paris; Department of Neurology
(G.A.), Hôpitaux Civils de Colmar; Department of Public Health (N.T., M.N.),
Hospices Civils de Lyon; and Department of Medicine (A.M.), Centre Leon Berard,
UNICANCER, Lyon, France.
BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune
encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE)
have poor functional outcomes and high mortality, the prognosis of
nonparaneoplastic cases has not been well studied.
METHODS: Patients with GABABR-AE from the French and the Dutch Paraneoplastic
Neurologic Syndromes Reference Centers databases were retrospectively included
and their data collected; the neurologic outcomes of paraneoplastic and
nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and
human leukocyte antigen (HLA) genotyping were performed in patients with
available samples.
RESULTS: A total of 111 patients (44/111 [40%] women) were enrolled, including
84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases
(cancer status was undetermined for 9 patients). Patients presented with
seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral
disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care
unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54
years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p <
0.001) and showed a different demographic distribution. Nonparaneoplastic
patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02),
were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p <
0.001), and were more frequently treated with second-line immunotherapy (11/18
[61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA
association was observed, although sample size was small (10 and 26 patients,
respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13
of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p =
0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last
follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after
adjustment for confounding factors but seemed to be negatively associated with
increased age and ICU admission. A better survival was associated with
nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs.
DISCUSSION: Nonparaneoplastic GABABR-AE involved younger patients without
associated KCTD16-abs and carried better neurologic and vital prognoses than
paraneoplastic GABABR-AE, which might be due to a more intensive treatment
strategy. A better understanding of immunologic mechanisms underlying both forms
is needed.
DOI: 10.1212/NXI.0000000000200229
PMCID: PMC11087025
PMID: 38657198 [Indexed for MEDLINE]
Conflict of interest statement: M.J. Titulaer has filed a patent, on behalf of
the Erasmus MC, for methods for typing neurologic disorders and cancer, and
devices for use therein, and has received research funds for serving on a
scientific advisory board of MedImmune LLC, for consultation at Guidepoint
Global LLC, for consultation at UCB, and for teaching colleagues by Novartis.
M.J. Titulaer has received an unrestricted research grant from Euroimmun AG and
from CSL Behring. M.J. Titulaer was supported by an Erasmus MC fellowship and
has received funding from the Netherlands Organization for Scientific Research
(NWO, Veni incentive), ZonMw (Memorabel program), and the Dutch Epilepsy
Foundation (NEF 14–19 and 19-08). M.W.J. Schreurs, J.M. de Vries, M.J. Titulaer,
M. Benaiteau, B. Joubert, and J. Honnorat of this publication are members of the
European Reference Network for Rare Immunodeficiency, Autoinflammatory, and
Autoimmune Diseases-Project ID No 739543 (ERN-RITA; HCP Erasmus MC). Go to
Neurology.org/NN for full disclosures.