Introduction
Auditory neuropathy, a condition first described by Starr et al.,Reference Starr, Picton, Sininger, Hood and Berlin1 is a disorder characterised by absent or severely abnormal auditory brainstem responses with intact outer hair cell function, as evidenced by evoked otoacoustic emissions (OAE) and/or cochlear microphonics. The aetiology of this disorder is multifactorial, involving genetic, congenital and acquired factors. Taking into consideration the heterogeneous and multifaceted nature of the condition, the label of auditory neuropathy has been expanded to ‘auditory neuropathy spectrum disorder’. The heterogeneous nature of the disorder adds to the problems associated with the development of a comprehensive assessment protocol for affected individuals. The main physiological pathology associated with neuropathic conditions of the vestibulocochlear nerve, particularly auditory neuropathy, is primary demyelination or axonal disease. It is highly probable that the vestibular nerve is involved in such disorders affecting the cochlear nerve, as both form part of the vestibulocochlear nerve.Reference Akdogan, Selcuk, Ozcan and Dere2
The vestibular branch of the vestibulocochlear nerve, which includes the superior and the inferior vestibular nerves, is involved in maintaining a sense of equilibrium. Other implicated structures include the vestibular nuclei, the semicircular canals and the central oculomotor system. The functioning of the superior vestibular nerve and the end organ it innervates, namely the semicircular canals, can be assessed using electronystagmography (ENG). Electronystagmography can also be employed to examine the vestibulo-ocular reflexes and subsystems of vestibulo-ocular reflexes. The status of the inferior vestibular nerve and the otolith organ it innervates, namely the saccule, can be assessed by means of vestibular-evoked myogenic potentials. In individuals with auditory neuropathy, vestibular evaluations are typically carried out using caloric and vestibular-evoked myogenic potential recordings. The present review examined the findings of vestibular tests in such individuals.
Electronystagmography findings
Starr et al. (1996) were the first to report on the functioning of the vestibular system in individuals diagnosed with auditory neuropathy.Reference Starr, Picton, Sininger, Hood and Berlin1 These authors described 10 such patients, 3 of whom showed horizontal nystagmus on lateral gaze and 2 others had absent responses to caloric vestibular testing. These five patients were also asymptomatic with regard to vestibular dysfunction. In addition to neuropathic changes in the vestibulocochlear nerve, all five patients showed evidence of a generalised peripheral neuropathy. This led the authors to suggest that the abnormal auditory and vestibular test results formed part of a generalised neuropathic disorder affecting both (vestibular and cochlear) components of the VIIIth cranial nerve.
In the same year, Kaga et al. reported on two patients diagnosed as having an ‘auditory nerve disease’.Reference Kaga, Nakamura, Shinogami, Tsuzuku, Yamada and Shindo3 These patients also complained of vestibular symptoms, and ice water caloric testing failed to elicit any nystagmus in either patient. The patients' performances in the central vestibular tests and the positional and positioning tests were normal. The results were attributed to slight involvement of the vestibular organs and brainstem, and a possible lesion of the cochlear nerve.
Konradsson described the results of vestibular assessment carried out on four children with severe sensorineural hearing loss and normal OAE.Reference Konradsson4 The children did not have any vestibular symptoms. An ENG battery was administered, which consisted of bithermal caloric tests as well as tests of pursuit, voluntary saccades and optokinetic nystagmus. The recordings of all tests were similar to those of normal individuals. The authors suggest that the patients may have had a pure auditory neuropathy affecting their auditory system without vestibular involvement.
Sheykholeslami et al. assessed three patients who fit the criteria for auditory neuropathy.Reference Sheykholeslami, Kaga, Murofushi and Hughes5 These patients also complained of balance disorders, and showed abnormal results with eyes closed on subsequent testing with the Romberg's, Mann's and stepping tests. Spontaneous nystagmus was not found in any patient, thereby ruling out central involvement of the vestibular tract. Caloric stimulation elicited horizontal nystagmus without vertigo in the right ear of one of the patients, but was otherwise ineffective at provoking responses. The authors concluded that, in patients with isolated auditory neuropathy, the vestibular branch of the VIIIth cranial nerve and its innervated structures can also be affected. They also provided evidence that the vestibular system may be affected in patients with non-progressive isolated auditory neuropathy. This led to their proposal of the term ‘cochlear neuropathy’ to characterise cases with involvement of only the auditory branch of the VIIIth cranial nerve and its innervations.
Fujikawa and Starr reported the incidence of abnormal peripheral vestibular test results in 14 individuals with auditory and peripheral neuropathies who had no symptoms of vestibular dysfunction.Reference Fujikawa and Starr6 Bilateral auditory neuropathies were identified in all of the patients, and eight of these had concomitant peripheral neuropathies too. Vestibular abnormalities were present in 9 of the 14 patients, 7 of whom had concomitant peripheral neuropathies. Five of those with vestibular abnormalities had absent responses and three had asymmetrical responses. The results for these five patients were within the normal range with regard to the sinusoidal tracking test, the optokinetic test and the gaze test. Saccadic test results were within the normal range for all 5 patients. The results indicate that certain types of degenerative peripheral neuropathies are associated with a neuropathy of the vestibular nerves. Of the two patients who had abnormal caloric responses without having peripheral neuropathies, one had a temperature-sensitive auditory neuropathy associated with a demyelinating disorder of the auditory nerve. The other patient had an isolated auditory neuropathy, and a younger sibling of this patient had an auditory neuropathy with normal vestibular test results. Together, these reports indicate variability with regards to the extent of vestibular nerve involvement in neuropathic lesions in patients with auditory neuropathy associated with peripheral neuropathy.
Starr et al. studied a family with hearing loss of the auditory neuropathy type associated with peripheral neuropathy.Reference Starr, Michalewski, Zeng, Fujikawa-Brooks, Linthicum and Kim7 The authors focused on the histopathological changes that occurred in the vestibular nerves, thereby enabling a correlation between the anatomical changes and the obtained clinical findings. Two members of the family had an absence of eye movements and no symptoms of vertigo when tested by caloric stimulation. The pathological findings indicated that the damage was related to the overall reduction in vestibular nerve endings between the receptor organ and the ganglion. In addition, the vestibular nerve was found to have a beaded appearance, which suggested incomplete remyelination. Examination also revealed fragmentation of the myelin layer with gaps almost equal to the diameter of the nerve fibre, along with distortion of the nerve structure. Such changes to the structure of the vestibular nerve could explain the absence of responses on caloric stimulation. The presence of beading along the distal portion of the vestibular nerve in the absence of extensive beading along the proximal portion suggested that the pathology may be restricted to the distal portion of the nerve rather than the central portion. Thus, the central oculomotor pathways may not have undergone such changes. This correlates with reports of normal functioning in patients with auditory neuropathy on saccade, gaze and optokinetic tests.Reference Sheykholeslami, Kaga, Murofushi and Hughes5, Reference Starr, Michalewski, Zeng, Fujikawa-Brooks, Linthicum and Kim7–Reference Sheykholeslami, Schmerber, Kermany and Kaga9
A subsequent case study by Sheykholeslami et al. revealed no involvement of the superior vestibular nerve and its end organ, the semicircular canal, in a patient with isolated auditory neuropathy.Reference Sheykholeslami, Schmerber, Kermany and Kaga9 Caloric stimulation elicited a normal response in the patient, with normal functioning on other central and peripheral ENG tests. This indicates that there is also a range of variability in terms of the vestibular system status of auditory neuropathy patients who do not present with peripheral neuropathy.
The presence of vestibular neuropathy in auditory neuropathy patients seems to be independent of associated neuropathic diseases. Abdel-Nasser et al. (2006) assessed 50 individuals with auditory neuropathy using a series of tests to evaluate vestibular functioning.Reference Abdel-Nasser, Elkhayat, Khalil and Mahmoud8 Bithermal caloric irrigation revealed that 30 per cent of these patients had bilaterally reduced caloric response, and 14 per cent had bilaterally absent caloric response. In total, 44 per cent of the patients had extensive bilateral peripheral vestibular lesions, as evidenced by the absence of responses to bilateral caloric stimulation. Of the 50 individuals assessed, only 18 per cent complained of dizziness and other vestibular symptoms. The patients also showed an absence of spontaneous, gaze-evoked, positional and positioning nystagmus. Oculomotor test results revealed normal saccade velocity, accuracy and latency. Eye-tracking and optokinetic tests were normal. Taken together, it can be inferred that the central vestibular connections are normal in individuals with auditory neuropathy, but peripheral nerve functioning is affected.
Certain types of degenerative peripheral neuropathies are associated with a neuropathy of the vestibular nerves. One such condition is neurosarcoidosis, wherein patients are found to have inflammatory demyelinating neuropathic changes of the vestibular, auditory and facial nerves, and a concomitant degeneration of the vestibular and cochlear sensory structures. The audiological profiles of such patients fit the criteria established for auditory neuropathy. Caloric stimulation failed to elicit nystagmus responses in such patients, indicating bilateral vestibular dysfunction.Reference Babin, Liu and Aschenbrener10, Reference von Brevern, Lempert, Bronstein and Kocen11 Frohman et al. described a patient with inflammatory demyelinating polyneuropathy, with fluctuating findings of oscillopsia and ataxia.Reference Frohman, Tusa, Mark and Comblath12 In addition, bithermal calorics were abnormally low. These results provide evidence that vestibular dysfunction occurs in association with certain types of degenerative neuropathies involving the peripheral nerves.
Akdogan et al. assessed three auditory neuropathy individuals aged between four and five years whose audiological profile yielded results typical of those found in individuals with auditory neuropathy.Reference Akdogan, Selcuk, Ozcan and Dere2 Caloric responses were reported to be normal in all three individuals assessed. The authors suggested that vestibular neuropathy was a late manifestation in patients with auditory neuropathy.
Kaga reported that ice water caloric stimulation failed to elicit any response on ENG in five auditory neuropathy patients, and vestibular-evoked myogenic potentials were also absent.Reference Kaga, Kaga and Starr13 These patients were therefore labelled as having ‘auditory-vestibular neuropathy’. Three other patients performed normally on the vestibular evaluations and were thereby diagnosed as having ‘auditory neuropathy only’. Similar findings have been reported in individuals with auditory neuropathy who have a genetic association.Reference Mizutari, Matsunaga, Inoue, Kaneko, Yagi and Namba14
Recently, Sharanya et al. (unpublished data) studied three patients diagnosed with auditory neuropathy who underwent an extensive vestibular assessment, which consisted of clinical tests of stability (Romberg's, Fukuda stepping test), vestibular-evoked myogenic potential recordings and a standard ENG test battery. All patients showed hypofunctional caloric responses and absent vestibular-evoked myogenic potentials. Two of the three patients were asymptomatic in terms of vestibular dysfunction. On the clinical tests of stability, two patients showed deviations to the right, while the remaining patient performed normally. The authors concluded that individuals with auditory neuropathy may have associated abnormality of the superior and inferior vestibular nerve. The authors also suggested that the absence of vestibular symptoms in individuals with auditory neuropathy may be due to compensatory changes that occur over time.
Vestibular-evoked myogenic potential findings
The study by Sheykholeslami et al. (2000) was one of the earliest to employ the use of vestibular-evoked myogenic potentials to obtain information on the status of the saccule and its innervations to the inferior vestibular nerve.Reference Sheykholeslami, Kaga, Murofushi and Hughes5 These authors assessed three individuals diagnosed with auditory neuropathy in the absence of peripheral neuropathy. Rectified vestibular-evoked myogenic potential recordings for 500 Hz, air-conducted tone stimuli were carried out. The vestibular-evoked myogenic potential responses were absent for all patients in both ears, which was suggestive of the involvement of the inferior vestibular nerve in addition to the auditory nerve.
The extent of involvement of the inferior vestibular nerve mimics the variability seen in the findings and auditory symptoms of patients with auditory neuropathy. In the case study by Sheykholeslami et al., the vestibular-evoked myogenic potential responses were normal in the right ear and absent in the left ear.Reference Sheykholeslami, Schmerber, Kermany and Kaga9 Those results, in conjunction with normal caloric responses in both ears, provided conclusive evidence of a unilateral sacculo-collic neuropathy accompanying bilateral auditory neuropathy. The authors noted that vestibular involvement could range from normal functioning to complete vestibular areflexia, and may implicate only one part of the vestibular apparatus, such as the sacculus or the innervated inferior vestibular nerve.
A study of individuals with auditory neuropathy by Kumar et al. indicated the absence of cervical vestibular-evoked myogenic potentials in 16 of the 20 ears assessed.Reference Kumar, Singh, Bharti, Sinha and Barman15 The authors reported that the vestibular-evoked myogenic potentials were either absent or prolonged in latency, and there was a reduction in amplitude in 80 per cent of the ears tested. The authors suggested that the term ‘acoustic neuropathy’ should be used to indicate those patients in whom only the acoustic nerve is affected, and the label ‘vestibuloacoustic neuropathy’ should be applied to those patients who also show involvement of the vestibular system. The absence of vestibular-evoked myogenic potentials could be attributed to the fact that the vestibular and cochlear branches are parts of the same VIIIth cranial nerve fibre bundle; it is likely that neuropathy in the cochlear branch of the nerve might extend to the vestibular branch.
A similar study by Sazgar et al. (2010) was carried out to investigate the role of the saccule and related neural pathways in auditory neuropathy.Reference Sazgar, Yazdani, Rezazadeh and Yazdi16 Eight patients (16 ears) with auditory neuropathy (aged from 21 to 45 years) were tested for vestibular-evoked myogenic potentials and the results were compared to a normal control group. Vestibular-evoked myogenic potentials were normal in three ears and abnormal in all others, including unrepeatable waveforms in four ears and absent vestibular-evoked myogenic potentials in nine ears. The findings of the study indicated a dysfunction of the inferior vestibular nerve and its end organ (the saccule) in auditory neuropathy. They also highlighted the subclinical nature of the vestibular dysfunction. The authors suggested that the vestibular symptoms reflected both the bilateral distribution of the disorder as well as the possible slow progression of vestibular neuropathy.
A study by Akdogan et al. was the only study found that focused on cervical vestibular-evoked myogenic potential recordings in children with auditory neuropathy.Reference Akdogan, Selcuk, Ozcan and Dere2 Three children aged between four and five years were assessed for sacculo-collic pathway paucity. The results revealed an absence of vestibular-evoked myogenic potential responses in two of the three patients, suggesting a sacculo-collic dysfunction in the two patients. These results, in conjunction with the presence of normal caloric responses in all three patients, led the authors to suggest the use of a comprehensive test battery involving both vestibular-evoked myogenic potential recording and ENG, in order to rehabilitate patients and reduce deficits at an early age.
• It is likely that auditory neuropathy involves both the vestibular and cochlear nerve
• In most, the site of the lesion may be restricted to the peripheral vestibular nerve
• There is variability in the findings of various vestibular tests in auditory neuropathy patients
• Vestibular symptoms are typically absent, probably due to the bilateral distribution of the disorder and compensatory changes
To summarise, it is likely that a neuropathic condition in individuals with auditory neuropathy may additionally involve the vestibular nerve (as well as the cochlear nerve). There is high variability in both the audiological and vestibular findings of auditory neuropathy patients. Furthermore, in most cases of auditory neuropathy, pathology is restricted to the peripheral vestibular system and does not affect the central oculomotor system. The vestibular test results of auditory neuropathy patients may help elucidate our understanding of the related pathophysiology.
