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Brain white matter changes in asymptomatic carriers of Leber’s hereditary optic neuropathy

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Abstract

Objective

Subclinical abnormalities, including microangiopathy, swelling of nerve fibers, visual field abnormalities and visual functional impairments had been reported in Leber’s hereditary optic neuropathy (LHON) carriers. The purpose of this study was to investigate microstructural changes of brain white matter in asymptomatic LHON carriers using DTI and tract-based spatial statistics (TBSS).

Methods

DTI and neuro-ophthalmologic measurements were acquired in 14 LHON carriers and 15 gender- and age-matched healthy controls, and diffusion metrics, including fractional anisotropy (FA), axial (AD), radial diffusion (RD) and mean diffusion (MD) were calculated. Intergroup differences in diffusion metrics were compared regressing out potential nuisance covariates of age and gender. A correlation analysis was performed to test associations between abnormal neuro-ophthalmologic measures and diffusion metrics while controlling the effects of age and gender.

Results

Compared to healthy controls, LHON carriers showed a weak increase of thickness of the retinal nerve fiber layer (RNFL) of the right inferior quadrant (F = 5.22, p = 0.032, before multiple comparison correction). LHON carriers exhibited widespread decreased FA value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi and left superior longitudinal fasciculus), increased RD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, bilateral superior longitudinal fasciculi and bilateral uncinate fasciculi) and increased MD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, left superior longitudinal fasciculus and bilateral uncinate fasciculi). Moreover, these changed diffusion metrics were not correlated with age, gender, LHON mutations and retinal measures in LHON carriers.

Conclusion

Our results show microstructural alterations in brain white matter in asymptomatic LHON carriers, indicating that LHON-related genetic mutations themselves might result in occult white matter alterations in the brain.

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Abbreviations

AD:

Axial diffusivity

RD:

Radial diffusivity

FA:

Fractional anisotropy

TBSS:

Tract-based spatial statistics

LHON:

Leber’s hereditary optic neuropathy

mtDNA:

Mitochondrial DNA

RNFL:

Retinal nerve fiber layer

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Funding

This work was supported by the Natural Science Foundation of China (81771818 and 81425013), and National Key Research and Development Program of China (2018YFC1314300 and 2017YFC0909201), and Natural Science Foundation of Tianjin (17JCYBJC29200).

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Authors and Affiliations

  1. Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China

    Miaomiao Long, Hao Ding, Wen Qin & Chunshui Yu

  2. Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China

    Miaomiao Long

  3. Department of Radiology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450003, Henan, China

    Ling Wang, Qin Tian & Dapeng Shi

  4. Henan Key Laboratory for Medical Imaging of Neurological Disease, Zhengzhou, 450003, Henan, China

    Ling Wang, Qin Tian & Dapeng Shi

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  1. Miaomiao Long
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  2. Ling Wang
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  3. Qin Tian
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  4. Hao Ding
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  5. Wen Qin
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  6. Dapeng Shi
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  7. Chunshui Yu
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Correspondence to Wen Qin, Dapeng Shi or Chunshui Yu.

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This research has been approved by the Ethics Committees of Tianjin Medical University General Hospital, Tianjin First Central Hospital, Zhengzhou University People's Hospital and Henan Provincial People's Hospital, and it has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consents from all subjects or their parents (for children less than 18 years old) were obtained before the study.

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Long, M., Wang, L., Tian, Q. et al. Brain white matter changes in asymptomatic carriers of Leber’s hereditary optic neuropathy. J Neurol 266, 1474–1480 (2019). https://doi.org/10.1007/s00415-019-09284-2

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  • DOI: https://doi.org/10.1007/s00415-019-09284-2

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