Auditory Brainstem Pathology in Autism Spectrum Disorder: A Review.

Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.

Severe auditory processing disorder secondary to viral meningoencephalitis.

OBJECTIVE: To describe auditory function in an individual with bilateral damage to the temporal and parietal cortex. DESIGN: Case report. STUDY SAMPLE: A previously healthy 17-year old male is described who sustained extensive cortical injury following an episode of viral meningoencephalitis. He developed status epilepticus and required intubation and multiple anticonvulsants. RESULTS: Serial brain MRIs showed bilateral temporoparietal signal changes reflecting extensive damage to language areas and the first transverse gyrus of Heschl on both sides. The patient was referred for assessment of auditory processing but was so severely impaired in speech processing that he was unable to complete any formal tests of his speech processing abilities. Audiological assessment utilizing objective measures of auditory function established the presence of normal peripheral auditory function and illustrates the importance of the use of objective measures of auditory function in patients with injuries to the auditory cortex. CONCLUSIONS: Use of objective measures of auditory function is essential in establishing the presence of normal peripheral auditory function in individuals with cortical damage who may not be able to cooperate sufficiently for assessment utilizing behavioral measures of auditory function.

Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project.

BACKGROUND: Maternal thyroid autoantibodies during pregnancy have been implicated in neurodevelopmental delays, including early childhood cognitive deficits. We evaluated whether maternal autoantibodies to thyroid peroxidase (TPOaAbs) during late pregnancy were associated with childhood intelligence quotient (IQ) scores in their offspring and how the children's TPOaAb-associated sensorineural hearing loss (HL) might affect the result. METHODS: We evaluated banked third-trimester sera corresponding to 1,733 children for whom childhood cognitive test scores and audiology data were available. The mothers and their children participated in the National Institutes of Health (NIH)-sponsored Collaborative Perinatal Project (CPP) that ran from 1959 to 1974. RESULTS: A modest, statistically significant, effect of TPOaAbs on cognitive performance observed at 4 y of age lessened in both magnitude and P value by the age of 7 y. Children with sensorineural HL (SNHL) had lower IQ scores at both ages. CONCLUSION: Our data suggest that the reported effect of maternal TPOaAbs on IQ may involve early developmental delays or transient effects rather than permanent deficits. Reports associating TPOaAbs directly with IQ may reflect a portion with unexamined TPOaAb-associated SNHL. Whether the TPOaAb-associated SNHL is in the neurodevelopmental pathway of later cognitive delays or is independently associated with IQ requires investigation in other studies.

Prenatal antecedents of newborn neurological maturation.

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24 to 38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the first weeks after birth were examined. Prenatal measures included fetal heart rate (FHR) variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity, FHR variability, and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation.

Prevalence of hearing loss and ear morbidity among adolescents and young adults in rural southern Nepal.

A cross-sectional survey was conducted among 3646 persons, 15 to 23 years of age, in the southern plains District of Sarlahi, Nepal, to assess the prevalence and severity of hearing loss and middle-ear dysfunction, and adverse effects of hearing loss on social integration. Between 2006 and 2008, subjects were enumerated and underwent otoscopic, tympanometric, and audiometric evaluations at central sites in villages. Hearing loss was diagnosed in subjects who failed a hearing screening and exhibited an average air conduction threshold value greater than or equal to 30 dBHL in the worse ear. Clinically, 32.8% of subjects exhibited a dull or retracted tympanic membrane, and 18% had abnormal tympanometry. Nearly 12% failed the hearing screening test, among whom more than half, or 6.1% overall, had hearing loss. Hearing-impaired subjects were six- to eight-fold (ORs, with 95% CIs excluding 1.0) more likely to report problems in hearing usual sounds or communicating with other people. Among young adults living in southern Nepal, hearing loss is common, and associated with social disability.

Maternal thyroid autoantibodies during the third trimester and hearing deficits in children: an epidemiologic assessment.

Elevated maternal thyroid autoantibodies during pregnancy are linked to infertility, miscarriage, and neurodevelopmental deficits such as in cognitive function. It has not been established whether autoantibodies to thyroid peroxidase are associated with sensorineural hearing loss (SNHL). The authors tested stored third-trimester maternal serum specimens of 1,736 children for thyroid peroxidase autoantibodies (TPOaAb) by using an enzyme-linked immunosorbent assay technique. The children participated at the Baltimore, Maryland, site of the Collaborative Perinatal Project, which enrolled pregnant women in 1959-1965. An audiology examination was administered to the children at 8 years of age and was used to identify cases of SNHL. Compared with 4.3% of the other children, 22.7% of the children whose mothers had elevated TPOaAb (> or =62.5 IU/ml) had SNHL. The difference was significant after controlling for maternal race, age, and hypothyroidism (exact prevalence odds ratio = 7.5, 95% confidence interval: 2.4, 23.3). When a lower cutoff of TPOaAb > or =31.25 IU/ml was used, there continued to be an association with SNHL (exact prevalence odds ratio = 5.7, 95% confidence interval: 2.1, 15.6). The direction and magnitude of the association were similar when an alternative case definition of SNHL was used. These data suggest that antenatal exposure to maternal TPOaAb during the third trimester of pregnancy is associated with impaired auditory development.

Auditory function in adrenomyeloneuropathy.

Auditory brainstem responses (ABR), ipsilateral and contralateral acoustic reflexes and the masking level difference for speech (MLD) were studied in 29 patients with adrenomyeloneuropathy (AMN). Abnormalities were seen for all ABR components with Waves V and III affected to the greatest degree. For male patients with AMN, the I-III, III-V and I-V interpeak latency intervals were abnormal for a majority of patients. For female patients with AMN, the I-V and III-V interpeak latency intervals were abnormal for a majority of patients with the I-III interval less affected. Contralateral acoustic reflexes were elevated or absent for approximately 50% of ears. Ipsilateral acoustic reflexes were abnormal for 25% of ears. MLDs were significantly reduced in 72% of patients. When considered in terms of the earliest ABR wave abnormality, the earlier components of the ABR (i.e., Waves III and I) were the initial components impaired for the majority of ears. Word recognition in quiet was relatively unimpaired for all subjects. Despite the presence of marked ABR abnormalities, patients with AMN denied the presence of significant difficulty hearing.

Audiological findings in osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is an inherited bone and connective tissue disorder associated with the lifelong occurrence of frequent fractures following even mild trauma. Hearing loss is frequently reported in patients with OI. PURPOSE: This investigation is a retrospective study of measurements of tympanometry, acoustic reflexes, and transient evoked otoacoustic emissions in a sample of patients with OI grouped according to age. The purpose of the study was to examine the relationship between the type of OI, age, and audiological findings in a sample of individuals with OI. RESEARCH DESIGN: The study examined the correlation between audiometric measures, hearing loss of all types, and type of OI. STUDY SAMPLE: Forty-one patients with OI were included in the study. The patients were divided into two groups for analysis: one group less than 20 years of age (n=21) and the other group aged 20 and over (n=20). RESULTS: Hearing loss of all etiologies was observed in 62% of ears. Sensorineural or mixed hearing loss was observed in 41% and conductive hearing loss in 21% of ears. Results indicate that the younger patients with OI were subject to a greater risk of middle ear dysfunction associated with otitis media than is typical for children of comparable age. Tympanometric abnormalities associated with ossicular dysfunction were more often found in the older age group of patients. Hearing loss of all types was more prevalent in the older group of patients (88%) than in the younger patient group (38%). CONCLUSIONS: Hearing loss was not uncommon regardless of age. Therefore, close audiological monitoring of patients with OI is recommended across the age spectrum.

Construct validity of the auditory continuous performance test for preschoolers.

Development of diagnostic instruments directed toward neuropsychological assessment of preschoolers lags significantly behind those available for school-age children (DeWolfe, Byrne, & Bawden, 2000). This is particularly true for measures of executive function (EF). The Auditory Continuous Performance Test for Preschoolers (ACPT-P; Mahone, Pillion, & Hiemenz, 2001) is a computerized, Go-No-go test developed to measure selected EF skills in preschoolers. First, to determine whether performance on the ACPT-P is associated with hearing impairment, we compared performance of children with mild hearing loss (MHL) to controls on the ACPT-P, and measures of spatial working memory (SWM) and motor persistence (MP). There were no differences between performance of the MHL group and controls on any of these measures. Second, to examine the construct validity of the ACPT-P, we compared performance of 40 preschoolers with ADHD to 40 age- and sex-matched controls, using the ACPT-P to measure response preparation, sustained attention, and inhibitory control. We also compared these groups on measures of SWM and MP. The group with attention deficit hyperactivity disorder (ADHD) performed significantly worse than controls on the ACPT-P (omissions, mean response time, variability) and MP. The ACPT-P was correlated with the MP, but not with the SWM measure. Both the ACPT-P and the MP measures showed low to moderate correlations with parent ratings of behavior associated with ADHD. These findings support the use of performance-based assessment of executive control skills in preschoolers suspected of having ADHD. In this age group, the ACPT-P may be particularly useful in assessing sustained attention and response preparation and may complement behavior rating scales.

Characteristics of auditory agnosia in a child with severe traumatic brain injury: a case report.

We present a case that is unusual in many respects from other documented incidences of auditory agnosia, including the mechanism of injury, age of the individual, and location of neurological insult. The clinical presentation is one of disturbance in the perception of spoken language, music, pitch, emotional prosody, and temporal auditory processing in the absence of significant deficits in the comprehension of written language, expressive language production, or peripheral auditory function. Furthermore, the patient demonstrates relatively preserved function in other aspects of audition such as sound localization, voice recognition, and perception of animal noises and environmental sounds. This case study demonstrates that auditory agnosia is possible following traumatic brain injury in a child, and illustrates the necessity of assessment with a wide variety of auditory stimuli to fully characterize auditory agnosia in a single individual.

Age and task parameters in continuous performance tests for preschoolers.

66 children (M=56.2 mo., SD=10.9), recruited from preschool and daycare centers, were administered two continuous performance tests, one auditory and one visual. Both tests utilized a format with one target and one nontarget. Interstimulus interval was fixed at 1350 msec. for the visual test and 5000 msec. for the auditory test. The visual test produced greater rates of omission and commission errors than the auditory test. Age was significantly related to mean reaction time and response variability for both tests; however, the visual test produced an unexpected pattern of increasing response time across age groups. On both tests omission rates improved significantly with age, while commission rates were consistent across ages 3-6 years. When considering continuous performance test paradigms for preschoolers, 3-yr.-olds may need at least a 4000-msec. interstimulus interval to make a choice for the stimulus cue. Hits following an interstimulus interval shorter than 1400 msec. may reflect younger preschoolers' response to a previous stimulus.

Speech processing disorder in neural hearing loss.

Deficits in central auditory processing may occur in a variety of clinical conditions including traumatic brain injury, neurodegenerative disease, auditory neuropathy/dyssynchrony syndrome, neurological disorders associated with aging, and aphasia. Deficits in central auditory processing of a more subtle nature have also been studied extensively in neurodevelopmental disorders in children with learning disabilities, ADD, and developmental language disorders. Illustrative cases are reviewed demonstrating the use of an audiological test battery in patients with auditory neuropathy/dyssynchrony syndrome, bilateral lesions to the inferior colliculi, and bilateral lesions to the temporal lobes. Electrophysiological tests of auditory function were utilized to define the locus of dysfunction at neural levels ranging from the auditory nerve, midbrain, and cortical levels.

Sensorineural Hearing Loss following Carbon Monoxide Poisoning.

A case study is presented of a 17-year-old male who sustained an anoxic brain injury and sensorineural hearing loss secondary to carbon monoxide poisoning. Audiological data is presented showing a slightly asymmetrical hearing loss of sensorineural origin and mild-to-severe degree for both ears. Word recognition performance was fair to poor bilaterally for speech presented at normal conversational levels in quiet. Management considerations of the hearing loss are discussed.

Hearing loss in osteogenesis imperfecta: characteristics and treatment considerations.

Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

Effects of sedation on auditory brainstem response in Rett syndrome.

Prolongation of the I-V interpeak latency intervals have been reported in Rett syndrome and other neurodevelopmental disorders. It has been suggested that the use of sedation may account for differences in the interpeak latency intervals when comparisons are made across diagnostic groups if sedated control groups are not used for the basis of comparison. This study examined the effects of sedation on auditory brainstem response interpeak latency intervals (i.e., I-III, III-V, and I-V) in two groups: (1) a group with Rett syndrome who were positive for mutations in the MECP2 gene and (2) a group negative for mutations in the MECP2 gene but who were severely to profoundly delayed with other causes of mental retardation. To further assess the effects of sedation, a third group of sedated and nonsedated female participants, taken from an in-house normative auditory brainstem response database was also included. An analysis of variance indicated (1) longer I-V interpeak latency intervals in the sedated participants with Rett syndrome; (2) longer III-V interpeak latency intervals in the mutation-positive participants as compared to non-Rett syndrome, mutation-negative participants; and (3) no significant effects of sedation on the I-III, III-V, or I-V interpeak latency intervals among the normative group participants, according to t tests. The findings suggest a possible biological basis for the discrepancy in the literature on auditory brain stem responses in Rett syndrome, and warrant cautious interpretation of auditory brainstem responses findings in sedated subjects with Rett syndrome, as well as in those with mental retardation and seizures.

Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb.

Infectious agents have been implicated as triggers of autoimmunity. Prospective epidemiologic studies of infection with specific pathogens and the subsequent elevation of specific autoantibodies are difficult and costly to conduct. As a result, a solid body of evidence regarding this theoretically intriguing connection remains to be accrued. We studied term sera from 1807 pregnancies in 1591 women for whom IgG status for cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, herpes simplex virus type 2, and/or Toxoplasma gondii was available from prior analyses. We tested the sera (masked regarding infectious status) for autoantibodies to thyroid peroxidase (TPOaAb) and then unmasked and linked them. Adjusted for other cofactors, prior infection with T. gondii was associated significantly with the elevation of TPOaAb, whereas seropositivity for other infections was not. Negative and positive findings for suspected triggers of autoimmunity should be reported to build the evidentiary basis needed to advance our understanding of the disease process. The positive association observed between prior infection with T. gondii and the elevation of TPOaAb is supported by an almost simultaneous study. These findings require further investigation. We believe that if T. gondii is in fact confirmed to trigger or enhance a TPOaAb response, the most likely mechanism involved is the bystander effect.

Prevalence of hearing loss in Rett syndrome.

This study examined the auditory status of females with Rett syndrome (RS) using auditory brainstem response (ABR) testing and measures of acoustic admittance. Prevalence of hearing impairment in 81 female patients (age range 1 year 3 months to 39 years 8 months; mean age 8 years 7 months, SD 6 years 4 months) was evaluated with ABR measurements. If the ABR latencies at 20dB nHL exceeded those of the normative group, a slight hearing loss was diagnosed. For ABR thresholds in the range 30 to 40dB nHL, a mild hearing loss was determined; moderate hearing loss was diagnosed for ABR thresholds in the range 50 to 60dB nHL. Bilateral hearing loss was found in 16 (19.3%) patients and unilateral hearing loss in 13 (16%) patients. Bilateral hearing loss of moderate degree was found in one patient. No patient was found with severe hearing loss (ABR threshold of 70dB nHL and above) in either ear. Slight hearing loss was found in 10.5% of ears (17 of 162), mild hearing loss in 14.2% of ears(23 of 162), and moderate hearing loss in 3.1% of ears (5 of 162). In 72.2% of ears (117 of 162), findings indicated the presence of normal peripheral auditory sensitivity. Prevalence of sensorineural hearing loss was 17.3% (28 of 162). Evidence of conductive involvement (conductive and mixed hearing loss) was observed in 9.9% of ears (16 of 162). In this cross-sectional study, the prevalence of hearing loss was increased in older RS participants and in those with seizures requiring the use of anticonvulsants. Neither the type of hearing loss nor the presence of preserved speech seemed to be correlated with the type of mutation in methyl-CpG-binding protein 2 (MeCP2) gene that is associated with RS.