Potential lesson from a model-based exploration on treatment effect heterogeneity of mal de débarquement syndrome.

Background: A central vestibular neural mechanism known as velocity storage may be inappropriately conditioned in mal de débarquement syndrome (MdDS), a rare chronic vestibular disorder with a continuous false sensation of self-motion described as non-spinning vertigo. Visual-vestibular therapy approaches designed to recondition the three-dimensional properties of velocity storage have yielded much clinical success, but not without limitations. An alternative therapeutic approach, designed to attenuate the contribution of malfunctioning velocity storage in higher-order neural processing, has also yielded positive results, but at a lower success rate. We sought a possible explanation for the latter shortcoming using a mathematical model. Methods: The three-dimensional orientation properties of velocity storage can be modeled as a dynamical system using a 3 × 3 system matrix. For normal upright, the system matrix is diagonal, with its eigenvectors aligning with the head-fixed roll, pitch, and yaw axes, and the yaw eigenvector with gravity. A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical. We manipulated the velocity storage's yaw time constant and output weight. Results: The model predicted that attenuating the velocity storage contribution could exaggerate the pull sensation. Conclusion: The present model-based exploration points to a possible weakness in the MdDS treatment approach focused on velocity storage attenuation, while likely beneficial otherwise. When a pulling sensation is present, the treatment protocol may need to be supplemented with another approach that specifically counters this problem, such as optokinetic stimulation.