Dysautonomia in anti-Hu paraneoplastic neurological syndromes
Macarena Villagrán-García, Antonio Farina, Jérôme Honnorat
Background and objectives Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia.
Methods Patients with anti-Hu antibodies diagnosed in the study centre (1990–2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified.
Results Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P=0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P<0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P=0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P=0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P=0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P=0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P=0.032). Patients with cardiovascular dysautonomia dying=/-1 year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement.
Discussion Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent.