Hypertrophic Degeneration of the Inferior Olive Yields Erroneous Internal Estimates of Direction of Gravity (P02.255)

Abstract

Objective: To investigate the role of the inferior olive (IO) for estimating direction of gravity. Background Central graviceptive pathways (CGP) connect the vestibular nuclei with cerebellar, brainstem and cortical areas. Acute lesions along the CGP lead to ocular torsion, skew deviation and subjective visual vertical (SVV) tilt. The IO is interconnected with the contralateral dentate nucleus and the ipsilateral red nucleus. Disruption of the central tegmental tract connecting the red nucleus with the IO may interfere with estimating direction of gravity. Design/Methods: We assessed the SVV in a 65yo man with a pontomesencephalic hemorrhage that included the medial vestibular nuclei, the right superior and lateral vestibular nucleus, the right interstitial nucleus of Cajal, the medial longitudinal fasciculus and central tegmental tract bilaterally. SVV was assessed at 16 days and 4 months after hemorrhage. Initially, he presented with gait ataxia, horizontal gaze palsy, impaired upgaze, and left-sided sensorimotor impairment. After four months he developed a vertical pendular nystagmus and increased gait ataxia. MR-imaging revealed a hypertrophic degeneration of the right IO. Results: Whereas SVV adjustments obtained at day 16 deviated 3.7° ipsilesional, large contralesional (-15.2°) deviations were found after four months. Conclusions: A shift from ipsilesional to contralesional SVV deviations in the presence of a hypertrophic degeneration of the IO was observed. We hypothesize that disrupted inhibitory GABA-ergic input from the red nucleus to the IO results in synchronized oscillations of IO neurons. These synchronized oscillations are signaled to the cerebellum, which results in a loss of inhibitory control that is normally provided through this pathway. This loss of inhibition could lead to hyperactivity of the dentate nucleus contralateral to the affected IO and consequently to a SVV tilt to the side of the overactive dentate nucleus. Such a mechanism would be in accordance to previous reports describing SVV tilts contralateral to an inhibited dentate nucleus. Supported by: Swiss National Science Foundation (3200B0-105434 and 32003B_130163/1), the Betty and David Koetser Foundation for Brain Research, Zurich, Switzerland, and the Center of Integrative Human Physiology, University of Zurich, Switzerland. Disclosure: Dr. Tarnutzer has nothing to disclose. Dr. Palla has nothing to disclose. Dr. Marti has nothing to disclose. Dr. Schuknecht has nothing to disclose. Dr. Straumann has nothing to disclose.