一側末梢前庭障害における前庭代償の神経可塑性メカニズムと治療戦略

抄録

Unilateral peripheral vestibular lesions cause a reduction in neural activity within the ipsi-lesional medial vestibular nucleus (ipsi-MVe), resulting in both static and dynamic asymmetries in vestibulo-ocular and vestibulo-spinal reflexes. These asymmetries manifest as spontaneous nystagmus, postural deviation, oscillopsia, and an unsteady gait. However, these behavioral deficits recover over time through a process known as vestibular compensation, which can be divided into static and dynamic phases.

The initial phase of static vestibular compensation involves plastic changes in the cerebello-vestibular and vestibular commissural inhibitory pathways, which lead to suppression of neurons in the contra-lesional medial vestibular nucleus (contra-MVe) and help restore symmetrical resting activity of MVe neurons at low levels. A decrease in the frequency of spontaneous nystagmus serves as an indicator of this initial compensation process. Short-term administration of diazepam, a GABA_A receptor agonist, accelerated this initial process in rats. Accordingly, short-term administration of diazepam is recommended for the treatment of acute vertigo in patients with unilateral vestibular dysfunction.

In the late phase of static vestibular compensation, the resting activity of the ipsi-MVe neurons gradually recovers due to changes in the cell membrane properties, which enhance intervestibular nuclear activity to near-normal levels without suppressing contra-MVe neurons. Reduction of MK801-induced Fos-positive neurons in the contra-MVe reflects this late compensation process. Long-term administration of betahistine, a histamine H₃ receptor antagonist, accelerated the late compensation process in rats. Accordingly, long-term administration of betahistine is recommended for the treatment of subacute vertigo in patients showing no compensation for unilateral vestibular dysfunction.

Dynamic vestibular compensation involves restoration of neuronal sensitivity to head motion via synaptic plasticity mechanisms, such as long-term potentiation and commissural sprouting. This process reinstates dynamic reflexes and is facilitated by early mobilization and vestibular rehabilitation exercises. These are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction.