Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

Characterization of vertigo and hearing loss in patients with Fabry disease

“…An extension of latency as sign of a neurogenic or central pathology was found 12 times in cVEMPs and 13 times in oVEMPs. These results are comparable to a recently published study with a mixed-gender group of 36 Fabry patients [ 37 ]. For the first time, it was reported on pathological cVEMPs in 45% of the patients, also occurring in nonsymptomatic patients.…”

A patient with neuropathy and ataxia: what do I have to consider?

“…Therefore, vibration sense and position sense are mostly normal but there may be abnormalities in pain and temperature sensation. Despite this lack of large fiber involvement, Carmona et al [24] found evidence of objective vestibular dysfunction in approximately half of their patient cohort, and similarly approximately 60% had evidence of hearing loss on pure tone audiogram. In the aggregate, 70% of subjects had combined cochlear and vestibular dysfunction.…”

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype&ndash;phenotype correlations</p>

“…Hearing loss, tinnitus, and vertigo are more prevalent in patients with FD than in the age-matched general population,1,2,95 but the underlying etiology remains unclear in many patients 96. The age onset of FD-related neuro-otologic symptoms is earlier, and their clinical severity is higher in hemizygous males than in heterozygous females.…”