Neurodegenerative disease is an umbrella term for a range of heterogeneous disorders that result in the loss of structure and function of neurons, the building blocks of the nervous system. These diseases are generally progressive, incurable, and debilitating conditions that result in the degeneration and/or death of nerve cells.
The most utilized standard of measurement in the audiology toolbox is the audiogram. But when it comes to assessing neurodegenerative diseases, the audiogram may prove to be a rather blunt instrument. The cases of two children are discussed here; one diagnosed with Friedrich's ataxia (FA) and the other with Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS). Clinical features, auditory-vestibular assessment techniques, and management considerations of these neurodegenerative diseases are discussed.
CASE 1: FRIEDRICH'S ATAXIA
FA, the most common autosomal recessive (AR) inherited ataxia, is a genetic neurodegenerative movement disorder of unstable GAA trinucleotide expansion in the FXN gene on chromosome 9 (9q21.11). Normal trinucleotide repeats in the FXN gene are about 12 to 33. Patients with FA can present with seven to 1,500 repeats; the number of repeats correlates with the age of onset and severity of the disease.1 The FXN gene provides instructions for making the frataxin protein found in mitochondria. Low levels of frataxin can lead to increased levels of iron, which reacts with oxygen-forming free radicals. These free radicals result in iron toxicity-mediated oxidative tissue damage in cells.2
FA onset is typically around puberty, with slow progression and decreased life expectancy. It is characterized by gait/limb ataxia, poor balance/coordination, sensory loss, areflexia, dysarthria, dysphagia, scoliosis, muscle weakness or spasticity, hypertrophic cardiomyopathy, and diabetes (in about ~30% of patients).3 Sensorineural hearing loss and vision loss are also reported in later stages of the disease. The presence of neurological as well as non-neurological manifestations makes this condition a true multisystem disorder.1
Abnormal eye movements are a common and early sign. These can include fixation instability, impaired ocular pursuit, saccadic dysmetria and prolonged latencies, square wave jerks, and horizontal gaze-evoked nystagmus.1,4 Difficulty hearing in noise is often reported with abnormal auditory evoked responses, indicating an accompanying auditory neuropathy. Patients with FA who have auditory neuropathy exhibit speech errors that reflect an inability to perceive temporal (timing) cues in speech sounds, thereby affecting efficient speech processing.5,6 Auditory-vestibular symptoms worsen with disease progression, necessitating monitoring.
Maya, a 17-year-old girl, was seen for a hearing evaluation at our university audiology clinic as part of her FA workup. She was diagnosed with FA when she was 10 years old. Genetic testing revealed that one of Maya's two siblings was a carrier of FA while the other tested negative. Maya reported some difficulty hearing in noise. She had passed her newborn hearing screening as well as a hearing evaluation performed four years prior, when she was 13. Maya had cardiomyopathy, scoliosis, muscle spasticity, and significant balance/motor problems that required her to require assistance to walk.
Pure-tone audiometric test results revealed normal hearing sensitivity at all frequencies from 250 through 8,000 Hz bilaterally. Immittance measures revealed a normal tympanogram and ipsilateral acoustic reflex thresholds (ARTs) bilaterally. Contralateral ARTs were elevated/absent, which was atypical for Maya's age and hearing levels (see Table 1).7 Distortion product otoacoustic emissions (DPOAEs) were present bilaterally, indicating normal cochlear function at least up to the outer hair cell level. Word recognition scores in quiet were excellent. The QuickSin speech-in-noise test revealed an SNR loss of 3.5 dB (mild SNR loss), indicating a slight difficulty listening in noise compared with individuals with normal hearing.8 This finding was inconsistent with Maya's age and hearing sensitivity. It was, however, consistent with her reported symptoms of difficulty hearing in noise, indicating some level of difficulty with speech processing, a sign of possible auditory neuropathy.
Auditory brainstem response (ABR) testing was performed in a naturally relaxed state. Absolute/interwave values were recorded at borderline prolonged latencies, especially for waves III and V, with overall poor/fair morphology inconsistent with age and normal hearing sensitivity. No reversal of cochlear microphonic with polarity change was noted. Neural synchrony was maintained even at an increased stimulus rate of 91.2/sec. Figure 1 shows Maya's ABR test results; view complete audiometric results images online: https://bit.ly/3chlNy3.
An oculomotor exam, performed with infrared VNG goggles and software, was normal apart from small saccadic intrusions during pursuit and slightly prolonged saccade latencies. These types of findings have been previously reported in the literature on patients with FA.1,4,9 Abnormal oculomotor test results correspond to the known pathologic changes of FA and can be useful in the differential diagnosis from cerebellar atrophy.9
CASE 2: GBS
GBS is a rapidly progressive acute autoimmune demyelinating peripheral polyneuropathy characterized by symmetric limb weakness, tingling, and loss of tendon reflexes.10 It is a rare and complex multifactorial genetic/environmental disorder that can present after exposure to viral infections such as Zika and influenza11 and bacterial infections affecting the respiratory or digestive tracts; about one in 1,000 develop GBS following a Campylobacter jejuni gastroenteric infection.12 Initially, GBS affects the lower extremities, which can progress and result in paralysis.11 The involvement of the respiratory muscles can lead to difficulty breathing with associated anxiety. Most patients make a full recovery within a year, but some exhibit long-term problems. Recurrences have also been reported.13
Speech understanding difficulties, but not sensorineural hearing loss, have been reported in the literature.14 Patients with GBS can exhibit hidden hearing loss (HHL), most likely caused by transient Schwann cell loss.15 HHL is an auditory neuropathy with defective cochlear neurotransmission characterized by an abnormal auditory brainstem response (ABR) but normal pure-tone thresholds, making it generally undetectable by standard audiometry.15
MFS, a GBS variant, is characterized by a clinical triad of acute-onset gait ataxia, areflexia, and ophthalmoplegia. Facial and bulbar nerve palsies and respiratory failure are common. Most patients (over 80%) with MFS have a unique antibody; specific anti-ganglioside antibodies, especially IgG anti-GQ1b, that characterize this disorder.16
Jack, a 12-year-old boy with MFS, was seen at the audiology clinic of a nearby children's hospital for complaints of significant difficulties understanding speech. Jack was born full term, with no complications during his mother's pregnancy or his birth. He passed the newborn hearing screening. Prior to his MFS diagnosis, he was typically developing with no concerns for hearing. He had not attended school for a year due to complications of GBS.
At the first audiologic evaluation appointment, Jack was anxious, wheelchair-bound, and on a ventilator with a tracheal tube. His anxiety and fatigue as well as the ventilator noise presented a challenge to the audiologic assessment, and the resulting behavioral pure-tone responses were not considered reliable. A follow-up appointment was scheduled. At the second appointment, Jack used an FM system per the audiologist's recommendations. However, he continued to have difficulty understanding speech. Jack was taken off the ventilator, which aided in the pure-tone testing. He was found to have normal to slight hearing loss bilaterally, although the test reliability was still fair/poor, possibly with better true thresholds than recorded. Tympanograms were normal bilaterally at all appointments. Distortion product otoacoustic emission (DPOAE) testing done in the second appointment showed present DPOAEs bilaterally. Acoustic reflex testing showed absent acoustic reflexes bilaterally, which was inconsistent with Jack's age, hearing levels, and otoacoustic emissions test results. Word recognition and speech-in-noise tests could not be performed because of patient fatigue/reliability concerns. ABR performed during natural sleep revealed absent waveforms bilaterally regardless of stimulus polarity or intensity levels (see Fig.2). Jack's audiometric test results (view complete audiometric results images online: https://bit.ly/3chlNy3) and continued difficulty understanding speech even with an FM system was indicative of HHL reported for patients with GBS.15,17 Axons re-myelination is common with GBS, but may be defective in some cases,15 necessitating technological/other interventions.18
Physicians and audiologists should consider auditory-vestibular dysfunction in patients with neurodegenerative diseases even when peripheral hearing sensitivity is normal. For both of these cases, the audiogram indicated normal hearing sensitivity with present OAEs. However, tests that assessed the auditory nerve (ABR and ARTs) and central auditory processing abilities (speech-in-noise tests) showed subtle abnormalities that were inconsistent with normal peripheral hearing sensitivity but consistent with some degree of auditory neuropathy. In Maya's case, mild oculomotor abnormalities suggested central vestibular system involvement. Serial ABRs, speech-in-noise tests, and vestibular assessments are necessary to monitor disease progression, fall risk, and/or recovery of function.6,9 Management should occur on a case-by-case basis because of the heterogeneous nature of these diseases. Audiologic management could include low-gain hearing aids, FM systems, and cochlear implants if needed.18 Vestibular management could include vestibular therapy and ambulatory assistive devices as needed.