Vestibular compensation: Neural mechanisms and clinical implications for the treatment of vertigo

Abstract

After unilateral peripheral vestibular lesions, the neural activity of neurons in the ipsi-lesional medial vestibular nucleus (ipsi-MVe) are markedly decreased, resulting in static and dynamic asymmetries of the vestibulo-ocular and vestibulo-spinal reflexes. Consequently, static vestibular symptoms such as spontaneous nystagmus and postural deviation and dynamic vestibular symptoms such as oscillopsia and swaying gait are induced. However, these behavioral asymmetries gradually recover after the lesion. Progressive balance restoration is termed vestibular compensation, which is divided into two phases: static and dynamic. Static vestibular compensation is further divided into initial and late processes. In the initial process of static vestibular compensation after unilateral labyrinthectomy (UL) in rats, plastic changes in the cerebello-vestibular and vestibular commissural inhibitory pathways suppress neurons in the contra-lesional MVe (contra-MVe), resulting in the restoration of symmetrical resting activity of MVe neurons on both sides at low levels. The declining frequency of spontaneous nystagmus after UL is an index of the initial process, and short-term administration of diazepam, a GABA_A receptor agonist, has been shown to accelerate the 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 process of static vestibular compensation after UL in rats, the resting activity of ipsi-MVe neurons gradually recovers due to changes in cell membrane properties, resulting in the reinforcement of balanced intervestibular nuclear activities to nearly normal levels without the suppression of contra-MVe neurons. The declining number of MK801-induced Fos-positive neurons in contra-MVe after UL is an index of the late process, and long-term administration of betahistine, a histamine H₃ receptor antagonist, has been shown to accelerate the late process in rats. Accordingly, long-term administration of betahistine is recommended for the treatment of subacute vertigo in patients who were not compensated for unilateral vestibular dysfunction. In the process of dynamic vestibular compensation after UL, the sensitivity of ipsi-MVe neurons to head velocity and acceleration is restored due to synaptic changes such as long-term potentiation and sprouting of commissures, resulting in the restoration of the dynamic vestibulo-ocular and vestibulo-spinal reflexes. To facilitate dynamic vestibular compensation, early ambulation and subsequent vestibular rehabilitation exercise are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction. Although vestibular compensation after bilateral vestibular loss is not expected, vestibular rehabilitation with a sensory-substitution strategy can improve imbalance in patients with bilateral vestibular lesions.

Keywords: Betahistine; Diazepam; Plastic change; Unilateral labyrinthectomy; Vestibular compensation; Vestibular rehabilitation.