Auditory Brainstem Response in a Child with Mitochondrial Disorder–Leigh Syndrome

Abstract

The mitochondrial disorder–Leigh syndrome is a neurodegenerative disorder often manifested with brainstem abnormalities. The case report highlights the auditory brainstem response in a child with medical findings suggestive of Leigh syndrome. The case report also emphasizes the importance of ruling out any underlying neural pathology before making a clinical impression in children with developmental delays.

Introduction

Leigh syndrome is a mitochondrial disorder manifested with neurological deterioration, demyelination, necrosis of neurons, vascular and capillary proliferation, and bilateral focal lesions in the brainstem, spinal cord, basal ganglia, and brain regions [1, 2]. It has a variable disease onset with the symptoms usually appearing between 3 and 12 months of age [1]. The most common clinical signs of Leigh syndrome include delayed developmental milestones of speech, language, and motor, hearing loss, cognitive decline, and other brainstem dysfunction signs [2].

The literature review on audiological findings in Leigh syndrome reported abnormal auditory brainstem response (ABR) [3–5] and it need not necessarily follow a typical pattern. Hence, the current case report aims to highlight the ABR findings in a child with Leigh syndrome.

Case Report

A 1-year-7-months-old female toddler diagnosed with global developmental delay with microcephalus was referred to the Department of Speech and Hearing, owing to a delay in speech and language skills and inconsistent response to sounds. Birth history indicated elderly pregnancy at the maternal age of 37 years and pre-term delivery. The child had undergone Magnetic Resonance Imaging (MRI) testing as suggested by the Paediatrician prior to the speech-language and audiological evaluation. However, the reports were not available during the time of evaluation.

The speech-language evaluation revealed a receptive language age of 18–20 months and an expressive language age of 12–14 months. The impression made was delayed speech and language skills secondary to global developmental delay. On audiological evaluation, behavioral observation audiometry revealed hearing thresholds between 40 and 50 dBHL across 500–4000 Hz frequencies and a speech detection threshold of 45 dBHL. Immittance audiometry findings showed As-type tympanogram in the right ear and A-type tympanogram in the left ear with ipsilateral acoustic reflexes present at 500 Hz, 1000 Hz, and 2000 Hz. Distortion product otoacoustic emissions (DPOAE) were present at high-frequency bands (> 3 kHz) and absent/reduced amplitude at low-frequency bands in both the ears (Fig. 1). Further, ABR was recorded using a click stimulus of rarefaction polarity with a repetition rate of 11.1/s presented at 90, 70, 50 and 30 dBnHL. In addition, one recording each of condensation and alternating polarities were recorded at 90 dBnHL to rule out cochlear microphonics.

Fig. 1.

Distortion product otoacoustic emission responses of right and left ears along with noise floor

ABR findings showed the presence of cochlear microphonics of short duration (< 1.5 ms) at 90 dBnHL in both the ears (Fig. 2). At 90 dBnHL, peaks-I, -II, and -III were prominent and peak-V was present with poor morphology in both the ears. The absolute latencies of peak-I were within normal limits and of peak-III and peak-V were prolonged in both the ears. Inter-peak latency differences were prolonged between peaks I–III, and I–V. Also, reduced peak V/I amplitude ratio (right ear: 1.00; left ear: 0.36) were observed in both the ears (Fig. 2). Further peaks-I, -II, -III, and -V were tracked till 30 dBnHL (Fig. 3). Overall prolonged latency, reduced amplitude and poor morphology were observed for peak-V across 70, 50, and 30 dBnHL.

Fig. 2.

Auditory brainstem response waveforms of the two ears at 90 dBnHL across three polarities (Click-R: Rarefaction; Click-A: Alternate; Click-C: Condensation). Dashed lines represent the Peak-I, -II, -III, and -V along with their latency (ms) and amplitude (µV) on a scale of 0.50 µV

Fig. 3.

Auditory brainstem response waveforms of the two ears at 70, 50 and 30 dBnHL for rarefaction (Click-R) polarity. Peaks-I, -II, -III, and -V are marked along with their latency (ms) and amplitude (µV) on a scale of 0.50 µV

Based on the ABR responses and a positive case history, the findings were suggestive of auditory pathway maturation delay. As the MRI reports were not available, the final diagnosis was kept inconclusive. The parents were advised for a follow-up with the medical reports. With the availability of MRI report, the ABR findings were re-analysed. The MRI findings revealed bilateral symmetrical altered signal intensity at putamen, both cerebral peduncles, dorsal aspect of the pons and medulla suggestive of mitochondrial disorder–Leigh syndrome. Hence, based on the MRI findings, the impression made was ‘indicative of brainstem dysfunction’. The child was recommended for a periodic follow-up to track the auditory status and to undergo speech and language intervention. Currently, the child is under medical line of treatment for Leigh syndrome.

Discussion

The ABR findings in the present case report were in correlation with the MRI report which indicated the presence of brainstem dysfunction. The ABR peaks-I and -II are generated from the auditory nerve, peaks-III from cochlear nucleus, peak-IV from superior olivary complex, cochlear nucleus and the nucleus of the lateral lemniscus, and peak-V from lateral lemniscus and inferior colliculus [6] which are housed in the pons region of brainstem [7]. Thus, the ABR findings in the present study indicated intact peripheral auditory nerve function, and brainstem dysfunction.

The ABR findings of the current study were in consensus with Yoshinaga [4] who reported prolonged I–III and I–V inter-peak latencies and prolonged absolute latency of peak-V in 7 months to 4 year old children diagnosed with Leigh syndrome. Further, Kaga [3] reported presence of peak-I and absence of peak-V, which was indicative of cortical form of Leigh syndrome in three children aged between 8 and 15 years 9 months. However, the probability of a transient auditory neuropathy spectrum disorder in the ABR recording of a child with Leigh syndrome was also reported by Yuvaraj [5]. Additionally, when the current case report with unrevealed MRI findings was presented to a group of audiologists for open discussion in a national forum, most of the audiologists suspected an auditory pathway maturation delay. Therefore, in the absence of radiological findings, there would be a greater likelihood of misdiagnosing the above findings as auditory pathway maturation delay, particularly in the context of a global developmental delay.

However, based on the current findings and literature evidence, the abnormalities of the ABR waveform could be dependent on the severity of the Leigh syndrome. It was difficult to compare whether the auditory functions of this child have been deteriorated or is in the phase of improvement with the medical interventions since the baseline audiological findings were unavailable. Thus, it is recommended that any child with global developmental delay or abnormal ABR findings should be monitored closely to rule out the underlying pathology if any.

Author Contributions

PSP, RG, EKJ, and SPS are involved in data collection. PSP, RG, and SPS are involved in writing the manuscript.

Funding

No funding was received.

Declarations

Conflict of interest

The authors have no conflict of interest.

Consent for Publication

Informed consent from the mother was obtained for case report submission.

Informed Consent

Informed consent was obtained from the participant’s parent.