NADH improves AIF dimerization and inhibits apoptosis in iPSCs-derived neurons from patients with auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment involving disruptions to inner hair cells (IHCs), ribbon synapses, spiral ganglion neurons (SGNs), and/or the auditory nerve itself. The outcomes of cochlear implants (CI) for ANSD are variable and dependent on the location of lesion sites. Discovering a potential therapeutic agent for ANSD remains an urgent requirement. Here, 293T stable transfection cell lines and patient induced pluripotent stem cells (iPSCs)-derived auditory neurons carrying the apoptosis inducing factor (AIF) p.R422Q variant were used to pursue a therapeutic regent for ANSD. Nicotinamide adenine dinucleotide (NADH) is a main electron donor in the electron transport chain (ETC). In 293T stable transfection cells with the p.R422Q variant, NADH treatment improved AIF dimerization, rescued mitochondrial dysfunctions, and decreased cell apoptosis. The effects of NADH were further confirmed in patient iPSCs-derived neurons. The relative level of AIF dimers was increased to 150.7 % (P = 0.026) from 59.2 % in patient-neurons upon NADH treatment. Such increased AIF dimerization promoted the mitochondrial import of coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4), which further restored mitochondrial functions. Similarly, the content of mitochondrial calcium (mCa2+) was downregulated from 136.7 % to 102.3 % (P = 0.0024) in patient-neurons upon NADH treatment. Such decreased mCa2+ levels inhibited calpain activity, ultimately reducing the percentage of apoptotic cells from 30.5 % to 21.1 % (P = 0.021). We also compared the therapeutic effects of gene correction and NADH treatment on hereditary ANSD. NADH treatment had comparable restorative effects on functions of ANSD patient-specific cells to that of gene correction. Our findings offer evidence of the molecular mechanisms of ANSD and introduce NADH as a potential therapeutic agent for ANSD therapy.

The audiovestibular profile of Brown-Vialetto-Van Laere syndrome.

BACKGROUND: Brown-Vialetto-Van Laere syndrome, a rare disorder associated with motor, sensory and cranial nerve neuropathy, is caused by mutations in riboflavin transporter genes SLC52A2 and SLC52A3. Hearing loss is a characteristic feature of Brown-Vialetto-Van Laere syndrome and has been shown in recent studies to be characterised by auditory neuropathy spectrum disorder. METHOD: This study reports the detailed audiovestibular profiles of four cases of Brown-Vialetto-Van Laere syndrome with SLC52A2 and SLC52A3 mutations. All of these patients had auditory neuropathy spectrum disorder. RESULTS: There was significant heterogeneity in vestibular function and in the benefit gained from cochlear implantation. The audiological response to riboflavin therapy was also variable, in contrast to generalised improvement in motor function. CONCLUSION: We suggest that comprehensive testing of vestibular function should be conducted in Brown-Vialetto-Van Laere syndrome, in addition to serial behavioural audiometry as part of the systematic examination of the effects of riboflavin.

Retro-labyrinthine Lesion Site Detected by Galvanic Vestibular Stimulation Elicited Vestibular-evoked Myogenic Potentials in Patients with Auditory Neuropathy.

OBJECTIVE: Auditory neuropathy (AN) is a unique pattern of hearing loss with preservation of hair cell function. The condition is characterized by the presence of otoacoustic emissions (OAE) or cochlear microphonic (CM) responses with severe abnormalities of the auditory brainstem response (ABR). The vestibular branches of the VIII cranial nerve and the structures innervated by it can also be affected. However, the precise lesion sites in the vestibular system are not well characterized in patients with AN. METHODS: The air-conducted sound (ACS) vestibular-evoked myogenic potentials (VEMPs) and galvanic vestibular stimuli (GVS)-VEMPs were examined in 14 patients with AN. RESULTS: On examination of VEMPs (n=14, 28 ears), the absent rates of ACS-cervical VEMP (cVEMP), ACS-ocular VEMP (oVEMP), GVS-cVEMP, GVS-oVEMP and caloric test were 92.9% (26/28), 85.7% (24/28), 67.9% (19/28), 53.6% (15/28), and 61.5% (8/13), respectively. Impaired functions of the saccule, inferior vestibular nerve, utricle, superior vestibular nerve, and horizontal semicircular canal were found in 25.0% (7/28), 67.9% (19/28), 32.1% (9/28), 53.6% (15/28) and 61.5% (8/13) patients, respectively. On comparing the elicited VEMPs parameters of AN patients with those of normal controls, both ACS-VEMPs and GVS-VEMPs showed abnormal results in AN patients (such as, lower presence rates, elevated thresholds, prolonged latencies, and decreased amplitudes). CONCLUSION: The study suggested that patients with AN often have concomitant vestibular disorders. Retro-labyrinthine lesions were more frequently observed in this study. GVS-VEMPs combined with ACS-VEMPs may help identify the lesion sites and facilitate detection of areas of vestibular dysfunction in these patients.

Clinical characteristics of patients with unilateral auditory neuropathy.

OBJECTIVE: To analyze the clinical characteristics of patients with unilateral auditory neuropathy (UAN), and to provide guidance for future clinical diagnosis and research. METHODS: Patients who were clinically diagnosed with UAN from 2004 to 2019 were included. Clinical characteristics, audiological features, imaging findings, genetic test results and management effect were summarized and followed. RESULTS: A total of 44 patients [mean age, 4.35 ± 4.39 years; 22 (50.00%) males and 22 (50.00%) females] were enrolled for analyses. Among the 38 patients who were tested by pure-tone or behavioral audiometry, the degree of hearing loss of the affected ear was characterized as mild in 2 ears (5.26%), moderate in 5 (13.16%), severe in 9 (23.68%) and profound in 22 (57.89%). For the 44 contralateral ears, 33 (75.00%) showed normal hearing and 11 (25.00%) presented with sensorineural hearing loss. Auditory brainstem responses were absent or abnormal in all 44 affected ears, while otoacoustic emissions and/or cochlear microphonics were present. Among the 18 patients who underwent magnetic resonance imaging (MRI), 7 (38.89%) presented cochlear nerve deficiency (CND). Nineteen candidate variants were found in 12 patients among the 15 UAN patients who were conducted targeted gene capture and next generation sequencing. Thirty patients were followed up by telephone to investigate their management effect. CONCLUSIONS: Our study demonstrates comprehensive audiological features of patients with UAN to improve the clinical understanding and diagnosis. Some patients with UAN could show ipsilateral CND and MRI is essential to evaluate if the nerve is deficient. No pathogenic variants that directly related to the pathogenesis of UAN have been found in this study currently.

Central auditory maturation and behavioral outcomes after cochlear implantation in prelingual auditory neuropathy spectrum disorder related to OTOF variants (DFNB9): Lessons from pilot study.

The cortical auditory evoked potential (CAEP)-based P1 component acts as a biomarker for cochlear implantation (CI) outcomes in children with auditory neuropathy spectrum disorder (ANSD). To date, early intervention primarily before the age of two years and six months of CI usage is necessary and sufficient to achieve age-appropriate cortical maturation and good prognosis. However, varying degrees of neural dyssynchrony, resulting from the etiological heterogeneity of ANSD, may preclude uniform application of this hypothesis to ensure auditory cortical maturation. Thus, a focused evaluation of those carrying OTOF variants, which may be the salient molecular etiology of prelingual ANSD, would circumvent the issue of heterogeneity. Here, we sought to provide a much better understanding of the brain perspectives (i.e., P1 maturation) in OTOF-associated ANSD subjects and set the stage for an optimal strategy to enhance language development. We conducted a preliminary study comprising 10 subjects diagnosed with OTOF-related ANSD who underwent CI by a single surgeon and subsequently underwent measurements of the P1 component. We observed that DFNB9 subjects who received CI after 2 years of age exhibited "absent" or "anomalous" P1 components that correspond to delayed language development. However, timely implantation, as early as 12 months of age per se, might be insufficient to achieve age-appropriate cortical maturation of DFNB9 in cases with six to seven months of device use. This suggests the importance of sustained rehabilitation in DFNB9 than in other etiologies. Indeed, an additional follow-up study showed that a reduction in P1 latency was linked to an improvement in auditory performance. Collectively, our results suggest that central auditory maturation and successful outcome of CI in DFNB9 may have more demanding requirements, that is, earlier implantation and more sustained rehabilitation. We believe that the current study opens a new path toward genome-based neuroimaging in the field of hearing research.

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Cochlear implantation in auditory neuropathy spectrum disorders: role of transtympanic electrically evoked auditory brainstem responses and serial neural response telemetry.

OBJECTIVE: To evaluate the utility of pre-operative transtympanic electrically evoked auditory brainstem responses and post-operative neural response telemetry in auditory neuropathy spectrum disorder patients. METHODS: Four auditory neuropathy spectrum disorder patients who had undergone cochlear implantation and used it for more than one year were studied. All four patients underwent pre-operative transtympanic electrically evoked auditory brainstem response testing, intra-operative and post-operative (at 3, 6 and 12 months after switch-on) neural response telemetry, and out-patient cochlear implant electrically evoked auditory brainstem response testing (at 12 months). RESULTS: Patients with better waveforms on transtympanic electrically evoked auditory brainstem response testing showed superior performance after one year of implant use. Neural response telemetry and electrically evoked auditory brainstem response measures improved in all patients. CONCLUSION: Inferences related to cochlear implantation outcomes can be based on the waveform of transtympanic electrically evoked auditory brainstem responses. Robust transtympanic electrically evoked auditory brainstem responses suggest better performance. Improvements in electrically evoked auditory brainstem responses and neural response telemetry over time indicate that electrical stimulation is favourable in auditory neuropathy spectrum disorder patients. These measures provide an objective way to monitor changes and progress in auditory pathways following cochlear implantation.

Auditory testing outcomes with hearing aids in patients with auditory neuropathy spectrum disorder.

OBJECTIVE: The objective of this study is to evaluate the audiologic outcomes with hearing aids in pediatric patients with auditory neuropathy spectrum disorder (ANSD) using the Infant Toddler-Meaningful Auditory Integration Scale (IT-MAIS), and the Ling 6 Sound Test (Ling 6). STUDY DESIGN: Case series. SETTING: Single tertiary care academic medical center. SUBJECTS AND METHODS: All pediatric patients with a confirmed diagnosis of ANSD on Auditory Brainstem Response (ABR) testing who presented to a single tertiary medical center between September 2008 and September 2018 were included. Only patients that underwent Infant Toddler-Meaningful Auditory Integration Scale (IT-MAIS) and/or Ling 6 Sound Test (Ling 6) were included in the study. Audiologic testing performed after cochlear implantation was excluded. RESULTS: 60 pediatric patients with ANSD were analyzed. There were 10 patients included in the study with documented hearing aid use who underwent IT-MAIS and/or Ling 6 testing. Average IT-MAIS score improved by 20.4% after initial or extended trial of amplification. Similarly, average Ling 6 score improved from 3.6 to 4.8 after initial or extended trial of amplification. The four patients who did not receive amplification had higher average IT-MAIS and Ling 6 scores. CONCLUSION: In most children with ANSD, IT-MAIS and Ling 6 Sound Test scores improved with initial hearing aid use and over time with extended hearing aid use. Long-term prospective, multi-institutional studies are needed to determine the impact of the natural history of ANSD, comorbidities, and socioeconomic variables on auditory function testing results in children with ANSD using hearing aids.

Subcortical deafness as a subtype of auditory agnosia after injury of bilateral auditory radiations caused by two cerebrovascular accidents - normal auditory brainstem responses with I-VII waves and abolished consciousness of hearing.

BACKGROUND: In central auditory disorders caused by damage of the cerebral hemispheres, there are cortical deafness and auditory agnosia. Although clinical cases of cortical deafness have been reported, little is known about the hearing problems and localized lesions associated with cortical deafness. AIMS/OBJECTIVES: The aims of our research are to elucidate lesion sites associated with cortical deafness and to clarify why patients with cerebral lesions are not aware of any sound at all. MATERIALS AND METHODS: Three patients diagnosed as having total loss of hearing participated in this study. We conducted pure-tone audiometry, speech audiometry, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), and brain magnetic resonance imaging (MRI) to diagnose cortical deafness with aphasia tests of these patients. RESULTS: Our studies showed that waves VI and VII as well as waves I to V have normal peak latencies in ABRs in all three patients. In brain MRI, we found complete damage of proximal parts of bilateral auditory radiations in the three patients. CONCLUSIONS: We propose 'subcortical deafness' as a subtype of auditory agnosia.

Alterations of functional connectivity in auditory and sensorimotor neural networks: A case report in a patient with cortical deafness after bilateral putaminal hemorrhagic stroke.

RATIONALE: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. PATIENT CONCERNS: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. DIAGNOSES: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. INTERVENTIONS: The patient underwent in-patient stroke rehabilitation therapy for 2 months. OUTCOMES: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. LESSONS: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.

Left Ear Hearing Predicts Functional Activity in the Brains of Patients with Alzheimer's Disease Dementia.

OBJECTIVES: To determine whether central speech processing ability, as measured by hearing in noise, differs between right and left ears in adults with Alzheimer's disease related dementia (AD) as well as whether differences in central speech processing ability correlate with an fMRI-based measurement of global functional brain connectivity. METHODS: This prospective study was carried out at a tertiary referral center. Patients with an AD diagnosis and pure tone averages 40 dB HL or better were included. They were examined using resting-state fMRI and underwent central audiometric testing using the Dichotic Sentence Identification Test (DSI), the Dichotic Digits Test (DD), and the Synthetic Sentence Identification Test (SS), which test hearing in noise. DSI scores were correlated with resting-state fMRI connectivity between 361 distinct gray matter brain regions of interest (ROIs). Average global connectivity was calculated as mean functional connectivity between an ROI and the other 360 regions, a quantitative marker representing overall functional connectivity in the brain. RESULTS: Sixteen subjects had adequate fMRI and hearing data. The average age was 71.5 years old (±6.0). The average DSI score for the left ear was 40% (±34%) compared to 90% (±10%) in the right ear (P < .001). No difference between ears was noted on the DD. SS does not differentiate between ears, but worsening scores were noted with increasing background noise. Of the fMRI ROIs, 269 of the 361 had multiple comparison corrected significant correlations between global connectivity and DSI of the left ear (P = .004, r = .673), and all 269 showed higher functional connectivity for individuals with higher left DSI score. No correlations between DSI of the right ear and functional connectivity were found. CONCLUSIONS: Correlation was noted between left sided DSI and functional connectivity in patients with AD. Auditory input from the left ear was more susceptible to impairment, suggesting that side-specific auditory input may influence central auditory processing.

Case studies in neuroscience: cortical contributions to the frequency-following response depend on subcortical synchrony.

Frequency-following responses to musical notes spanning the octave 65-130 Hz were elicited in a person with auditory neuropathy, a disorder of subcortical neural synchrony, and a control subject. No phaselocked responses were observed in the person with auditory neuropathy. The control subject had robust responses synchronized to the fundamental frequency and its harmonics. Cortical onset responses to each note in the series were present in both subjects. These results support the hypothesis that subcortical neural synchrony is necessary to generate the frequency-following response-including for stimulus frequencies at which a cortical contribution has been noted. Although auditory cortex ensembles may synchronize to fundamental frequency cues in speech and music, subcortical neural synchrony appears to be a necessary antecedent.NEW & NOTEWORTHY A listener with auditory neuropathy, an absence of subcortical neural synchrony, did not have electrophysiological frequency-following responses synchronized to an octave of musical notes, with fundamental frequencies ranging from 65 to 130 Hz. A control subject had robust responses that phaselocked to each note. Although auditory cortex may contribute to the scalp-recorded frequency-following response in healthy listeners, our results suggest this phenomenon depends on subcortical neural synchrony.

EABR measurements during cochlear implantation in one-year-old, infant, child, adult, and elderly patients.

BACKGROUND: Clinical application of electrically-evoked intracochlear auditory brainstem responses (eABRs) for evaluation of brainstem maturity or aging changes has not been well investigated. AIM/OBJECTIVE: We compare the eV latencies of intraoperative eABR measurements in one-year-olds, infants, children, adults, and the elderly, with the goal of investigating the changes in the brainstem auditory pathway due to development and aging. MATERIALS AND METHODS: We studied 58 ears of 51 patients who underwent cochlear implantation between 2013 and 2019 using MED-EL's Concerto or Synchrony implants with Flex28 or Flex soft electrodes. EABRs were recorded during cochlear implantation. The stimuli were delivered by the MED-EL Maestro to the apical, middle, and basal turn electrodes at stimulus levels 1000, 800, and 600 cu, with a pulse width of 30 µs. RESULTS: In eABRs recorded from electrodes installed at both the mastoid and nape, there was no difference in latency between age groups within each stimulus level. CONCLUSION AND SIGNIFICANCE: ABR latency was not affected by development after age one and aging of the brainstem auditory pathway. Our study will be useful as a control in identifying abnormal eABR wave configurations in patients with cochlear malformations, cochlear nerve deficiencies, or auditory neuropathy, regardless of age.

Mitochondrial Dysfunction and Therapeutic Targets in Auditory Neuropathy.

Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy is limited. Auditory neuropathies (AN) were proved to play a substantial role in SNHL recently, and spiral ganglion neuron (SGN) dysfunction is a dominant pathogenesis of AN. Auditory pathway is a high energy consumption system, and SGNs required sufficient mitochondria. Mitochondria are known treatment target of SNHL, but mitochondrion mechanism and pathology in SGNs are not valued. Mitochondrial dysfunction and pharmacological therapy were studied in neurodegeneration, providing new insights in mitochondrion-targeted treatment of AN. In this review, we summarized mitochondrial biological functions related to SGNs and discussed interaction between mitochondrial dysfunction and AN, as well as existing mitochondrion treatment for SNHL. Pharmaceutical exploration to protect mitochondrion dysfunction is a feasible and effective therapeutics for AN.

Utility of Acoustic Change Complex as an Objective Tool to Evaluate Difference Limen for Intensity in Cochlear Hearing Loss and Auditory Neuropathy Spectrum Disorder.

Purpose This study aimed to investigate usefulness of acoustic change complex (ACC) as an objective measure of difference limen for intensity (DLI) in auditory neuropathy spectrum disorders (ANSD) and cochlear hearing loss (CHL). Method The study used a multiple static group comparison research design. Twenty normal-hearing individuals (NH), 19 individuals with ANSD, and 23 individuals with CHL underwent DLI measurement using behavioral (psychoacoustic) techniques and ACC. For eliciting ACC, a 500-ms, 1,000-Hz pure tone was presented at 80 dB SPL. Additionally, six variants of this stimulus with intensity increments of 1, 3, 4, 5, 10, and 20 dB starting 250 ms after stimulus onset were used to elicit the ACC. Results The lowest intensity change that produced replicable and clearly identifiable ACC was referred as objective DLI. In comparison to NH and CHL, the behavioral as well as the objective DLI were significantly larger (poorer) in ANSD (p < .05). Significantly strong positive correlation existed between DLI obtained using behavioral and objective measures (p < .05). Conclusions ACC could be a useful objective tool to measure DLI in the clinical population, provided the individuals of the clinical population fulfill the prerequisite of the presence of Auditory Long Latency Responses. Supplemental Material https://doi.org/10.23641/asha.12560132.

An integrative approach for pediatric auditory neuropathy spectrum disorders: revisiting etiologies and exploring the prognostic utility of auditory steady-state response.

Auditory neuropathy is an important entity in childhood sensorineural hearing loss. Due to diverse etiologies and clinical features, the management is often challenging. This study used an integrative patient-history, audiologic, genetic, and imaging-based approach to investigate the etiologies and audiologic features of 101 children with auditory neuropathy. Etiologically, 48 (47.5%), 16 (15.8%), 11 (10.9%), and 26 (25.7%) children were categorized as having acquired, genetic, cochlear nerve deficiency-related, and indefinite auditory neuropathy, respectively. The most common causes of acquired and genetic auditory neuropathy were prematurity and OTOF mutations, respectively. Patients with acquired auditory neuropathy presented hearing loss earlier (odds ratio, 10.2; 95% confidence interval, 2.2-47.4), whereas patients with genetic auditory neuropathy had higher presence rate of distortion product otoacoustic emissions (odds ratio, 10.7; 95% confidence interval, 1.3-85.4). In patients with different etiologies or pathological sites, moderate to strong correlations (Pearson's r = 0.51-0.83) were observed between behavioral thresholds and auditory steady-state response thresholds. In conclusion, comprehensive assessments can provide etiological clues in ~75% of the children with auditory neuropathy. Different etiologies are associated with different audiologic features, and auditory steady-state responses might serve as an objective measure for estimating behavioral thresholds.

Evidence for independent peripheral and central age-related hearing impairment.

Deleterious age-related changes in the central auditory nervous system have been referred to as central age-related hearing impairment (ARHI) or central presbycusis. Central ARHI is often assumed to be the consequence of peripheral ARHI. However, it is possible that certain aspects of central ARHI are independent from peripheral ARHI. A confirmation of this possibility could lead to significant improvements in current rehabilitation practices. The major difficulty in addressing this issue arises from confounding factors, such as other age-related changes in both the cochlea and central non-auditory brain structures. Because gap detection is a common measure of central auditory temporal processing, and gap detection thresholds are less influenced by changes in other brain functions such as learning and memory, we investigated the potential relationship between age-related peripheral hearing loss (i.e., audiograms) and age-related changes in gap detection. Consistent with previous studies, a significant difference was found for gap detection thresholds between young and older adults. However, among older adults, no significant associations were observed between gap detection ability and several other independent variables including the pure tone audiogram average, the Wechsler Adult Intelligence Scale-Vocabulary score, gender, and age. Statistical analyses showed little or no contributions from these independent variables to gap detection thresholds. Thus, our data indicate that age-related decline in central temporal processing is largely independent of peripheral ARHI.

Cortical deafness of following bilateral temporal lobe stroke.

Cortical deafness is an extremely rare clinical manifestation that originates mainly from bilateral cortical lesions in the primary auditory cortex. Its main clinical manifestation is the bilateral sudden loss of hearing. Diagnosis is difficulty due to its rarity and similarity with other language and communication disorders, such as Wernicke's aphasia, auditory agnosia or verbal deafness. Herein, we present a case report of a young woman with a sudden bilateral loss of auditory comprehension. Initially, a psychiatric nature of the disorder was considered, but the persistence of the symptoms, lead to the diagnosis of cortical deafness secondary to bilateral ischemic lesions in both temporal lobes. Progressive improvement occurred and three months after the initial manifestations she manifested pure verbal deafness. Cortical deafness usually has a poor functional prognosis, with limited therapeutic options. Rehabilitation and speech therapy is recommended to improve the chance of patients achieving communication skills.

Acquired auditory neuropathy spectrum disorder after malaria treated with quinine.

Auditory neuropathy spectrum disorder (ANSD) can cause significant hearing impairment; it occurs when there is intact outer hair cell function in the inner ear, with a dyssynchronous neural response, thought to be due to dysfunction of the inner hair cells (IHCs), the synapse of the IHCs and the auditory nerve, or of the auditory nerve itself. This case report describes the onset of ANSD in a Malawian child after severe malaria treated with quinine. Diagnosis of ANSD was made by confirming the presence of otoacoustic emissions, together with the absence of auditory brainstem response and absent acoustic reflexes.

An unperceived acoustic stimulus decreases reaction time to visual information in a patient with cortical deafness.

Responding to multiple stimuli of different modalities has been shown to reduce reaction time (RT), yet many different processes can potentially contribute to multisensory response enhancement. To investigate the neural circuits involved in voluntary response initiation, an acoustic stimulus of varying intensities (80, 105, or 120 dB) was presented during a visual RT task to a patient with profound bilateral cortical deafness and an intact auditory brainstem response. Despite being unable to consciously perceive sound, RT was reliably shortened (~100 ms) on trials where the unperceived acoustic stimulus was presented, confirming the presence of multisensory response enhancement. Although the exact locus of this enhancement is unclear, these results cannot be attributed to involvement of the auditory cortex. Thus, these data provide new and compelling evidence that activation from subcortical auditory processing circuits can contribute to other cortical or subcortical areas responsible for the initiation of a response, without the need for conscious perception.