Abnormal Cerebral Blood Flow in Patients with Leber's Hereditary Optic Neuropathy

Overview

Journal Brain Imaging Behav

Publisher Springer

Specialties Neurology
Psychology
Radiology
Social Sciences

Date 2023 Jun 27

PMID 37368154

Authors

Ling Wang

Yi Ji

Hao Ding

Qin Tian

Ke Fan

Dapeng Shi

Chunshui Yu

Wen Qin

Affiliations

Soon will be listed here.

Abstract

Purpose: The study aimed to unravel abnormal cerebral blood flow (CBF) in patients with Leber's hereditary optic neuropathy (LHON) using arterial spin labeling (ASL) and to investigate the associations among disrupted CBF, disease duration, and neuro-ophthalmological impairment.

Methods: ASL perfusion imaging data was collected from 20 patients with acute LHON, 29 patients with chronic LHON, and 37 healthy controls. We used a one-way analysis of covariance to test the intergroup differences in CBF. Linear and nonlinear curve fit models were applied to explore the associations among CBF, disease duration, and neuro-ophthalmological metrics.

Results: Brain regions differed in LHON patients, including the left sensorimotor and bilateral visual areas (p < 0.05, cluster-wise family-wise error correction). Acute and chronic LHON patients demonstrated lower CBF in bilateral calcarine than the healthy controls. Chronic LHON had lower CBF in the left middle frontal gyrus and sensorimotor cortex, and temporal-partial junction than the healthy controls and acute LHON. A significant logarithmic negative correlation was shown between CBF of left middle frontal gyrus and disease duration. A significant linear positive correlation was found between retinal nerve fiber layer thickness and CBF in left middle frontal gyrus, and negative correlations between loss of variance and CBF in left middle frontal gyrus and sensorimotor cortex (p < 0.05, Bonferroni correction).

Conclusion: LHON patients exhibited reduced CBF in the visual pathway, sensorimotor and higher-tier cognitive areas. Disease duration and neuro-ophthalmological impairments can influence the metabolism of non-visual areas.

References

Alsop D, Detre J, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L . Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2014; 73(1):102-16. PMC: 4190138. DOI: 10.1002/mrm.25197. View

Anurova I, Renier L, De Volder A, Carlson S, Rauschecker J . Relationship Between Cortical Thickness and Functional Activation in the Early Blind. Cereb Cortex. 2014; 25(8):2035-48. PMC: 4494021. DOI: 10.1093/cercor/bhu009. View

Asanad S, Tian J, Frousiakis S, Jiang J, Kogachi K, Felix C . Optical Coherence Tomography of the Retinal Ganglion Cell Complex in Leber's Hereditary Optic Neuropathy and Dominant Optic Atrophy. Curr Eye Res. 2019; 44(6):638-644. DOI: 10.1080/02713683.2019.1567792. View

Balducci N, Savini G, Cascavilla M, La Morgia C, Triolo G, Giglio R . Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy. Br J Ophthalmol. 2015; 100(9):1232-7. DOI: 10.1136/bjophthalmol-2015-307326. View

Barbiroli B, Montagna P, Cortelli P, Iotti S, Lodi R, Barboni P . Defective brain and muscle energy metabolism shown by in vivo 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation. Neurology. 1995; 45(7):1364-9. DOI: 10.1212/wnl.45.7.1364. View

Barcella V, Rocca M, Bianchi-Marzoli S, Milesi J, Melzi L, Falini A . Evidence for retrochiasmatic tissue loss in Leber's hereditary optic neuropathy. Hum Brain Mapp. 2010; 31(12):1900-6. PMC: 6871150. DOI: 10.1002/hbm.20985. View

Bhoyroo R, Hands B, Caeyenberghs K, De Luca A, Leemans A, Wigley A . Association between Motor Planning and the Frontoparietal Network in Children: An Exploratory Multimodal Study. J Int Neuropsychol Soc. 2021; 28(9):926-936. DOI: 10.1017/S1355617721001168. View

Blanke O, Landis T, Spinelli L, Seeck M . Out-of-body experience and autoscopy of neurological origin. Brain. 2003; 127(Pt 2):243-58. DOI: 10.1093/brain/awh040. View

Borrelli E, Triolo G, Cascavilla M, La Morgia C, Rizzo G, Savini G . Changes in Choroidal Thickness follow the RNFL Changes in Leber's Hereditary Optic Neuropathy. Sci Rep. 2016; 6:37332. PMC: 5112509. DOI: 10.1038/srep37332. View

10.

Brugger P . Reflective mirrors: perspective-taking in autoscopic phenomena. Cogn Neuropsychiatry. 2006; 7(3):179-94. DOI: 10.1080/13546800244000076. View

11.

Burton H, Diamond J, McDermott K . Dissociating cortical regions activated by semantic and phonological tasks: a FMRI study in blind and sighted people. J Neurophysiol. 2003; 90(3):1965-82. PMC: 3705560. DOI: 10.1152/jn.00279.2003. View

12.

Burton H, Sinclair R, McLaren D . Cortical activity to vibrotactile stimulation: an fMRI study in blind and sighted individuals. Hum Brain Mapp. 2004; 23(4):210-28. PMC: 3697024. DOI: 10.1002/hbm.20064. View

13.

Carelli V, Carbonelli M, de Coo I, Kawasaki A, Klopstock T, Lagreze W . International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy. J Neuroophthalmol. 2017; 37(4):371-381. DOI: 10.1097/WNO.0000000000000570. View

14.

Chinnery P, Johnson M, Wardell T, Hayes C, Brown D, Taylor R . The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol. 2000; 48(2):188-93. View

15.

Collignon O, Charbonneau G, Lassonde M, Lepore F . Early visual deprivation alters multisensory processing in peripersonal space. Neuropsychologia. 2009; 47(14):3236-43. DOI: 10.1016/j.neuropsychologia.2009.07.025. View

16.

Collignon O, Dormal G, Albouy G, Vandewalle G, Voss P, Phillips C . Impact of blindness onset on the functional organization and the connectivity of the occipital cortex. Brain. 2013; 136(Pt 9):2769-83. DOI: 10.1093/brain/awt176. View

17.

Cui S, Yang L, Jiang H, Peng J, Shang J, Wang J . Clinical Features of Chinese Sporadic Leber Hereditary Optic Neuropathy Caused by Rare Primary mtDNA Mutations. J Neuroophthalmol. 2020; 40(1):30-36. DOI: 10.1097/WNO.0000000000000799. View

18.

dAlmeida O, Mateus C, Reis A, Grazina M, Castelo-Branco M . Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss. Neuroimage. 2013; 81:222-230. DOI: 10.1016/j.neuroimage.2013.05.032. View

19.

De Volder A, Bol A, Blin J, Robert A, Arno P, Grandin C . Brain energy metabolism in early blind subjects: neural activity in the visual cortex. Brain Res. 1997; 750(1-2):235-44. DOI: 10.1016/s0006-8993(96)01352-2. View

20.

Ebbesen C, Insanally M, Kopec C, Murakami M, Saiki A, Erlich J . More than Just a "Motor": Recent Surprises from the Frontal Cortex. J Neurosci. 2018; 38(44):9402-9413. PMC: 6209835. DOI: 10.1523/JNEUROSCI.1671-18.2018. View