Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

Abstract

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.

• Authors: Florian Lamblin, Jeroen Kerstens, Sergio Muñiz-Castrillo, Alberto Vogrig, David Goncalves, Veronique Rogemond, Geraldine Picard, Marine Villard, Anne-Laurie Pinto, Marleen H Van Coevorden-Hameete, Marienke A De Bruijn, Juna M De Vries, Marco Schreurs, Louise Tyvaert, Lucie Hopes, Jerome Aupy, Cecile Marchal, Dimitri Psimaras, Laurent Kremer, Veronique Bourg, Jean-Christophe G Antoine, Adrien Wang, Philippe Kahane, Sophie Demeret, Guido Ahle, Vicente Peris Sempere, Noemie Timestit, Mikail Nourredine, Aurelien Maureille, Marie Benaiteau, Bastien Joubert, Emmanuel Mignot, Maarten J Titulaer, Jerome Honnorat
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 11 Issue 3 Pg. e200229 (May 2024) ISSN: 2332-7812 [Electronic] United States
• PMID: 38657198 (Publication Type: Journal Article, Comparative Study, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, GABA-B
• Autoantibodies

Topics

• Humans
• Female
• Male
• Middle Aged
• Adult
• Aged
• Receptors, GABA-B (immunology)
• Encephalitis (immunology)
• Hashimoto Disease (immunology)
• Autoantibodies (cerebrospinal fluid, blood)
• Retrospective Studies
• Young Adult
• Paraneoplastic Syndromes, Nervous System (immunology)
• Aged, 80 and over