Inner ear involvement in multiple sclerosis: An underestimated condition?

The interest of the scientific community for associated symptoms in multiple sclerosis (MS) has grown in the last years. Audio-vestibular manifestations such as sudden sensorineural hearing loss (SSNHL) and acute vertigo are often reported in patients with MS; such conditions are mainly attributed to demyelination of the vestibulocochlear nuclei and temporal lobe, while the involvement of the vestibulocochlear nerve and inner ear is still debated and underestimated. ¹

Hearing impairment that mainly present as SSNHL, affects between 1% and 17% of MS patients ¹ and is commonly attributed to central nervous system demyelination. Vertigo affects from 7% to 30% of patients ² and is mostly attributed to demyelination of the vestibular nuclei, musculoskeletal weakness, and ocular diseases rather than to the labyrinth or vestibular nerve. However, there is growing pathophysiological evidence of the involvement of the inner ear and vestibulocochlear nerve in hearing loss and vertigo in MS patients.

The evidence of a unequivocal presence of macrophages in human temporal bones of patients with autoimmune disease, even at early stages of the disease, ³ supports the hypothesis that autoimmunity mechanisms in MS may also affect the inner ear; hair cells and auditory and vestibular spiral ganglion neurons may be subject to the attack of lymphocytes, and the resulting damage may manifest with SSNHL and acute vertigo.

Microglia, in its M1 phenotype, has been considered playing an important role in the processes of demyelination in MS. Temporal bone studies have identified microglia in the cochlea, showing its migration into the Internal Auditory Canal (IAC) until the inner ear. ⁴ M1 phenotype microglia could demyelinate cochlear and vestibular structures causing SSNHL or acute vertigo; such episodes may be temporary due to the relapsing–remitting phases of MS that alternatively activate the two different microglia phenotype (M1⇔M2).

The microglia demyelinating action on brain and medulla has been shown as White Matter Hyperintensities (WMH) in Magnetic Resonance Imaging (MRI) of patients with MS. The presence of WMHs in the IAC and in the cochlea has been previously demonstrated; ⁵ this supports the hypothesis that audiovestibular symptoms may be related to the effects of microglia on peripheral audiovestibular structures. Unfortunately, MRI does not have enough sensitivity to identify demyelization processes in the inner ear; such involvement could be instead explored with specific electrophysiological tests that are routinely used in audiological examination such as Auditory Brainstem Responses (ABR) and Vestibular Evoked Myogenic Potentials (VEMPs).

The role of the inner ear and vestibular cochlear nerve thereby determining hearing loss and vertigo in patients with MS is supported by current evidence. Audiovestibular symptoms in young subjects, especially when spontaneous recovery occurs, could represent an early sign of MS even when no demyelinated plaques are visible in the central nervous system; these subjects should always be evaluated with clinical, radiological, and electrophysiological tests to exclude peripheral incipient MS.