Multiple inflammatory cytokines correlate with the vestibular and oculomotor dysfunction in Fabry disease: a prospective, longitudinal study

Objectives: Vestibular and oculomotor abnormalities have been widely identified in Fabry disease (FD), with inflammation potentially playing an important role. We aim to investigate the expression of inflammatory cytokines (ICs) in FD patients and their relationship with the vestibular/oculomotor dysfunctions. Methods: This prospective observational study enrolled 40 FD patients. All 40 patients underwent the visuo-oculomotor examination, and 22 of them received the vestibulo-oculomotor examination. Plasma concentrations of 14 ICs were detected, including interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-β. Statistical analyses were made between different subgroups of patients. Results: (1) In the visuo-oculomotor examination, TNF-β was significantly higher in patients with prolonged saccade latency (1.61 ± 0.38 VS 1.14 ± 0.39, p=0.001) and hypometria (1.46 ± 0.39 VS 1.18 ± 0.48, p=0.043) than in patients without those abnormalities. The average saccade latency was positively correlated with the level of TNF-β (r=0.378, p=0.021), while the average saccadic accuracy was negatively correlated with the level of TNF-β (r=-0.333, p=0.044). IL-12p70 was significantly elevated in patients with defective pursuit compared to patients with normal pursuit (1.63 ± 0.20 VS 1.21 ± 0.54, p=0.040). (2) In the patients with vestibulo-oculomotor dysfunction, the plasma levels of IL-2 (3.40 ± 1.00 VS 2.13 ± 0.91, p=0.007), IL-17A (6.42 ± 3.59 VS 3.05 ± 2.13, p=0.021) and TNF-β (1.55 ± 0.41 VS 1.21 ± 0.37, p=0.030) were significantly elevated compared to the patients with normal vestibulo-oculomotor function. Conclusions: Inflammation-mediated pathological mechanism, especially TNF-β-related pathways, is associated to both central and peripheral vestibular dysfunction in FD patients.