Clinical manifestations of the anti-IgLON5 disease


Por: Gaig, C, Graus, F, Compta, Y, Hogl, B, Bataller, L, Bruggemann, N, Giordana, C, Heidbreder, A, Kotschet, K, Lewerenz, J, Macher, S, Marti, MJ, Montojo, T, Perez-Perez, J, Puertas, I, Seitz, C, Simabukuro, M, Tellez, N, Wandinger, KP, Iranzo, A, Ercilla, G, Sabater, L, Santamaria, J, Dalmau, J

Publicada: 2 may 2017
Resumen:
Objective: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. Methods: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. Results: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. Conclusions: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

Filiaciones:
Gaig, C:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

 Hosp Clin Barcelona, Multidisciplinary Sleep Disorders Unit, Barcelona, Spain

Graus, F:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

Compta, Y:
 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

 Hosp Clin Barcelona, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

Hogl, B:
 Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

Bataller, L:
 Hosp Univ & Politecn La Fe, Dept Neurol, Valencia, Spain

 Ctr Invest Biomed & Red Enfermedades Raras CIBERE, Valencia, Spain

Giordana, C:
 CHU Nice, Dept Movement Disorders & Neurol, Nice, France

Heidbreder, A:
 Univ Hosp Muenster, Div Sleep Med & Neuromuscular Disorders, Dept Neurol, Munster, Germany

Kotschet, K:
 St Vincents Hosp, Clin Neurosci, Melbourne, Vic, Australia

Lewerenz, J:
 Univ Ulm, Dept Neurol, Ulm, Germany

Macher, S:
 Med Univ Vienna, Dept Neurol, Vienna, Austria

Marti, MJ:
 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

 Hosp Clin Barcelona, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

Montojo, T:
 Ctr Hosp Luxembourg, Dept Neurol, Luxembourg, Luxembourg

Perez-Perez, J:
 Hosp Santa Creu & Sant Pau, Dept Neurol, Barcelona, Spain

Puertas, I:
 Hosp La Paz, Dept Neurol, Madrid, Spain

Seitz, C:
 Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, Mainz, Germany

Simabukuro, M:
 Univ Sao Paulo, Hosp Clin, Div Neurol, Sao Paulo, Brazil

Tellez, N:
 Hosp Clin Univ, Dept Neurol, Valladolid, Spain

Wandinger, KP:
 Univ Lubeck, Dept Neurol, Lubeck, Germany

 Univ Lubeck, Inst Neurogenet, Lubeck, Germany

 Univ Hosp Schleswig Holstein, Inst Clin Chem, Lubeck, Germany

Iranzo, A:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

 Hosp Clin Barcelona, Multidisciplinary Sleep Disorders Unit, Barcelona, Spain

Ercilla, G:
 Hosp Clin Barcelona, Dept Immunol, Barcelona, Spain

Sabater, L:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Ctr Invest Biomed & Red Enfermedades Raras CIBERE, Valencia, Spain

Santamaria, J:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Hosp Clin Barcelona, Dept Neurol, Barcelona, Spain

 Hosp Clin Barcelona, Multidisciplinary Sleep Disorders Unit, Barcelona, Spain

Dalmau, J:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain

 Ctr Invest Biomed & Red Enfermedades Raras CIBERE, Valencia, Spain

 Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

 Inst Catalana Rec & Estud Avancas ICREA, Barcelona, Spain
ISSN: 00283878
Editorial
LIPPINCOTT WILLIAMS & WILKINS, TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA, USA
Tipo de documento: Article
Volumen: 88 Número: 18
Páginas: 1736-1743
WOS Id: 000400330500011
ID de PubMed: 28381508
imagen Green Published

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