Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS.
OBJECTIVE
Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients.


METHODS
Basic scientific histopathological examination and quantitative mtDNA analysis of the temporal bone.


METHODS
Temporal bones were embedded in celloidin and sectioned for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht. For quantitative mtDNA analysis, total DNA from the membranous part of the inner ear was collected, amplified by polymerase chain reaction, and digested with the restriction enzyme. The percentage of mutant/total mtDNA was measured by the ratio of fluorescence intensity.


RESULTS
Histopathological examination revealed severe degeneration of the stria vascularis and degenerative change of spiral ganglion cells in both patients. The quantitative DNA studies showed that the proportion of mutant to wild-type mtDNA was similar in both histologically affected and histologically unaffected tissues within the inner ear.


CONCLUSIONS
Dysfunction of the stria vascularis and spiral ganglion cells causes sensorineural hearing loss in MELAS.
Takahashi
Katsumasa
K
Department of Otolarynology, Gunma University, Maebashi, Japan.
Merchant
Saumil N
SN
Miyazawa
Tetsuo
T
Yamaguchi
Toshikazu
T
McKenna
Michael J
MJ
Kouda
Hiroko
H
Iino
Yukiko
Y
Someya
Tsutomu
T
Tamagawa
Yuya
Y
Takiyama
Yoshihisa
Y
Nakano
Imaharu
I
Saito
Ken
K
Boyer
Philip
P
Kitamura
Ken
K
D000328:Adult; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D007758:Ear, Inner / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications; D006801:Humans; D017241:MELAS Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D013701:Temporal Bone / Q000737:chemistry / Q000473:pathology*
D004272:DNA, Mitochondrial