Audiological manifestations in mitochondrial encephalomyopathy lactic acidosis and stroke like episodes (MELAS) syndrome

Vandana, V.P.; Sankaran, Bindu Parayil; Kothari, Shawn; Govindaraj, Periyasamy; Taly, Arun B.; Gayathri, Narayanappa; Chiplunkar, Shwetha; Govindaraju, C.; Arvinda, H R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, Kumarasamy

doi:10.1016/j.clineuro.2016.04.024

Cited by 18 publications

(18 citation statements)

References 24 publications

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“…SNHL in patients with MELAS is commonly bilateral [ 5 , 6 , 19 , 20 ]; the unilateral form is present only in 2% of cases [ 4 , 17 ]. In both forms, SNHL affects high frequency in the onset (75%) and, then involves mild and low frequency [ 4 – 6 , 17 , 19 , 20 ]; in the remaining 25% of case SNHL affects all frequencies in its onset [ 4 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

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Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

Stadio

Pegoraro

Giaretta

et al. 2018

Orphanet J Rare Dis

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AimTo evaluate the feasibility of microRNAs (miR) in clinical use to fill in the gap of current methodology commonly used to test hearing impairment in MELAS patients.Material and methodA literature review was performed using the following keywords, i.e., MELAS, Hearing Loss, Hearing Impairment, Temporal Bone, Otoacustic Emission (OTOAE), Auditory Brain Response (ABR), and microRNA. We reviewed the literature and focused on the aspect of the temporal bone, the results of electrophysiological tests in human clinical studies, and the use of miR for detecting lesions in the cochlea in patients with MELAS.ResultsIn patients with MELAS, Spiral Ganglions (SG), stria vascularis (SV), and hair cells are damaged, and these damages affect in different ways various structures of the temporal bone. The function of these cells is typically investigated using OTOAE and ABR, but in patients with MELAS these tests provide inconsistent results, since OTOAE response is absent and ABR is normal. The normal ABR responses are unexpected given the SG loss in the temporal bone.Recent studies in humans and animals have shown that miRs, and in particular miRs 34a, 29b, 76, 96, and 431, can detect damage in the cells of the cochlea with high sensitivity. Studies that focus on the temporal bone aspects have reported that miRs increase is correlated with the death of specific cells of the inner ear.MiR − 9/9* was identified as a biomarker of human brain damage, miRs levels increase might be related to damage in the central auditory pathways and these increased levels could identify the damage with higher sensitivity and several months before than electrophysiological testing.ConclusionWe suggest that due to their accuracy and sensitivity, miRs might help monitor the progression of SNHL in patients with MELAS.

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Section: Resultsmentioning

confidence: 99%

“…In the study by Vandana et al [ 19 ], 6 children and 2 adults with MELAS were investigated; 3 out of 8 patients suffered from moderate to severe SNHL; in two cases the SNHL was subclinical; 1 presented a mild SNHL. All patients presented a down-ward sloping curve and OTOAE were absent in 50% of subjects.…”

Section: Resultsmentioning

confidence: 99%

Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

Stadio

Pegoraro

Giaretta

et al. 2018

Orphanet J Rare Dis

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“…Even in the absence of stroke-like episodes, MRI of patient 1 showed widespread hyperintensity on T2-weighted images of the bilateral frontal lobe, bilateral parietal lobe, basal ganglia, and corona radiata, indicating cerebral ischaemia, lacunar infarction, and cerebral atrophy. Interestingly, previous studies also reported hyperintensity of the bilateral basal ganglia and corona radiata on T2-weighted images in mt3243A > G mutation carriers, either with or without mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome [22–24]. Further research is warranted to investigate the relationship between T2-weighted images and the mt3243A > G mutation.…”

Section: Discussionmentioning

confidence: 96%

Rapid Detection of the mt3243A > G Mutation Using Urine Sediment in Elderly Chinese Type 2 Diabetic Patients

Zhang

Geng

et al. 2017

Journal of Diabetes Research

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Objective In this study, we aimed to identify mt3243A > G mutation carriers in a group of Chinese elderly type 2 diabetic patients by a rapid and noninvasive diagnostic system. Methods DNA was extracted from blood, saliva, and urine sediment samples. The mutation screening and quantitation of heteroplasmy were performed by high-resolution melting (HRM) curve and pyrosequencing, respectively. Patients with mt3243A > G mutation underwent a detailed audiometric, ophthalmologic, neurological, and cardiac examination. Results Two patients (2/1041) carrying the mt3243A > G mutation were detected among all type 2 diabetic patients. In patient 1, the heteroplasmy was 0.8%, 2.8%, and 14.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. In patient 2, the heteroplasmy was 5.3%, 8.4%, and 37.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. Both of the two patients showed hearing impairment. Abnormal ophthalmologic conditions and hyperintensity on T2-weighted magnetic resonance images were showed in patient 1. Conclusion The occurrence of mt3243 A > G mutation was 0.2% in Chinese elderly type 2 diabetic patients. Moreover, detection of mt3243 A > G mutation in urine sediment with high-resolution melting (HRM) curve and pyrosequencing is feasible in molecular genetic diagnosis.

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“…In the literature, it is often reported that the outcome of ABR testing is normal in these patients, even when they suffer from severe to profound SensoriNeural Hearing Loss (SNHL); however, some authors observed absence of ABR waves in mild forms of SNHL [1][2][3][4][5][6]. How can this disagreement in observations be explained?…”

Section: Editorialmentioning

confidence: 92%

“…The numerous mitochondrial mutations observed in the temporal bone of patients with MELAS [10][11] support the idea that the residual SGs do not function well enough to allow a correct transmission of the impulse, which in turn leads to an abnormal ABR. Arguably, the high ABR variability in MELAS patients reported in the literature [2,3,4,6] is due to the stochastic segregation of mitochondria during embryogenesis; the concentration of damaged mitochondria could differ among patients just due to …”

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confidence: 99%

Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

Arianna¹,

Antonietta²,

Dipietro³

et al. 2018

JOENTR

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We observed a MELAS patient who came to our Clinical Center for moderate SNHL. The ABR from this patient displayed waves (Figure 1) with amplitude and latency too reduced to be considered within the normal range, but not completely absent as it would be expected considering his auditory threshold in pure tone audiometry (PTA).In an attempt to explain this observation, we reviewed the literature on the temporal bone aspect of MELAS patients. Loss of Spiral Ganglions (SGs) and atrophy of Stria Vascularis (SV) are typical findings in temporal bone of patients with MELAS even when the Organ of Corti is entirely preserved.In SGs and SV mitochondria are abundant [7], as they are necessary to support the high metabolic functions of these structures. In MELAS, mitochondria that have been damaged (by deletion/mutation in their DNA) increase the Redox Oxidative Species (ROS) concentration [8] and cell apoptosis [9] which reduce the number of inner ear cells (SG, VS and Hair cells) and, cause a malfunction of the remaining cells.ABR reflects the way the auditory signal travels from the retrocochlear portion (synapse, SGs, cochlear nerve and cochlear nuclei) (Waves I, III) to the cortex (wave V); if all the structures in the retro-cochlear hearing pathways function correctly, the ABR displays normal amplitude and latency; but damage in even one of the structures causes abnormal ABR latency and/or amplitude, which in turn alter the overall signal shape.We think that the abnormal ABR of our patient can be explained by the altered functions of residual SGs, which cannot sufficiently amplify the signal to generate an actual ABR wave. The numerous mitochondrial mutations observed in the temporal bone of patients with MELAS [10][11] support the idea that the residual SGs do not function well enough to allow a correct transmission of the impulse, which in turn leads to an abnormal ABR. Arguably, the high ABR variability in MELAS patients reported in the literature [2,3,4,6] is due to the stochastic segregation of mitochondria during embryogenesis; the concentration of damaged mitochondria could differ among patients just due to

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Audiological manifestations in mitochondrial encephalomyopathy lactic acidosis and stroke like episodes (MELAS) syndrome

Cited by 18 publications

References 24 publications

Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

Rapid Detection of the mt3243A > G Mutation Using Urine Sediment in Elderly Chinese Type 2 Diabetic Patients

Auditory Brainstem Response and Hearing Loss in MELAS: Post Mortem Analysis of Temporal Bone to Explain Abnormal ABR

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