The Many Faces of Paediatric Mitochondrial Disease on Neuroimaging

Overview

Journal Childs Nerv Syst

Specialty Pediatrics

Date 2016 Jul 25

PMID 27449766

Citations 12

Authors

Fabian Baertling

Dirk Klee

Tobias B Haack

Holger Prokisch

Thomas Meitinger

Ertan Mayatepek

Jorg Schaper

Felix Distelmaier

Affiliations

Soon will be listed here.

Abstract

The knowledge about the genetic spectrum underlying paediatric mitochondrial diseases is rapidly growing. As a consequence, the range of neuroimaging findings associated with mitochondrial diseases became extremely broad. This has important implications for radiologists and clinicians involved in the care of these patients. Here, we provide a condensed overview of brain magnetic resonance imaging (MRI) findings in children with genetically confirmed mitochondrial diseases. The neuroimaging spectrum ranges from classical Leigh syndrome with symmetrical lesions in basal ganglia and/or brain stem to structural abnormalities including cerebellar hypoplasia and corpus callosum dysgenesis. We highlight that, although some imaging patterns can be suggestive of a genetically defined mitochondrial syndrome, brain MRI-based candidate gene prioritization is only successful in a subset of patients.

Citing Articles

MRI predictors of long-term outcomes of neonatal hypoxic ischaemic encephalopathy: a primer for radiologists.

Hung S, Tu Y, Hunter S, Guimaraes C Br J Radiol. 2024; 97(1158):1067-1077.

PMID: 38407350 PMC: 11654721. DOI: 10.1093/bjr/tqae048.

Leukodystrophy Associated with Mitochondrial Complex 1 Deficiency Due to Mutation in NUBPL Gene-An Unusual Follow-Up Finding.

Peter S B, Vandana G S Indian J Radiol Imaging. 2023; 33(1):132-135.

PMID: 36855717 PMC: 9968539. DOI: 10.1055/s-0042-1758195.

Malate dehydrogenase 2 deficiency is an emerging cause of pediatric epileptic encephalopathy with a recognizable biochemical signature.

Priestley J, Pace L, Sen K, Aggarwal A, Alves C, Campbell I Mol Genet Metab Rep. 2022; 33:100931.

PMID: 36420423 PMC: 9676216. DOI: 10.1016/j.ymgmr.2022.100931.

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Romero-Morales A, Robertson G, Rastogi A, Rasmussen M, Temuri H, McElroy G Development. 2022; 149(20).

PMID: 35792828 PMC: 9357378. DOI: 10.1242/dev.199914.

Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.

Laugwitz L, Seibt A, Herebian D, Peralta S, Kienzle I, Buchert R J Med Genet. 2021; 59(9):878-887.

PMID: 34656997 PMC: 9807242. DOI: 10.1136/jmedgenet-2021-107729.

References

Iizuka T, Sakai F, Suzuki N, Hata T, Tsukahara S, Fukuda M . Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome. Neurology. 2002; 59(6):816-24. DOI: 10.1212/wnl.59.6.816. View

Yatsuga S, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T . MELAS: a nationwide prospective cohort study of 96 patients in Japan. Biochim Biophys Acta. 2011; 1820(5):619-24. DOI: 10.1016/j.bbagen.2011.03.015. View

Brito S, Thompson K, Campistol J, Colomer J, Hardy S, He L . Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations. Front Genet. 2015; 6:102. PMC: 4369643. DOI: 10.3389/fgene.2015.00102. View

Danhauser K, Haack T, Alhaddad B, Melcher M, Seibt A, Strom T . EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum. Metab Brain Dis. 2016; 31(3):717-21. DOI: 10.1007/s11011-016-9793-2. View

Siddiq I, Widjaja E, Tein I . Clinical and radiologic reversal of stroke-like episodes in MELAS with high-dose L-arginine. Neurology. 2015; 85(2):197-8. PMC: 4515037. DOI: 10.1212/WNL.0000000000001726. View

Pauli W, Zarzycki A, Krzysztalowski A, Walecka A . CT and MRI imaging of the brain in MELAS syndrome. Pol J Radiol. 2013; 78(3):61-5. PMC: 3789935. DOI: 10.12659/PJR.884010. View

Baertling F, Schaper J, Mayatepek E, Distelmaier F . Teaching NeuroImages: rapidly progressive leukoencephalopathy in mitochondrial complex I deficiency. Neurology. 2013; 81(2):e10-1. DOI: 10.1212/WNL.0b013e31829a339b. View

Bricout M, Grevent D, Lebre A, Rio M, Desguerre I, de Lonlay P . Brain imaging in mitochondrial respiratory chain deficiency: combination of brain MRI features as a useful tool for genotype/phenotype correlations. J Med Genet. 2014; 51(7):429-35. DOI: 10.1136/jmedgenet-2013-102256. View

Holzerova E, Danhauser K, Haack T, Kremer L, Melcher M, Ingold I . Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration. Brain. 2015; 139(Pt 2):346-54. DOI: 10.1093/brain/awv350. View

10.

Lake N, Compton A, Rahman S, Thorburn D . Leigh syndrome: One disorder, more than 75 monogenic causes. Ann Neurol. 2015; 79(2):190-203. DOI: 10.1002/ana.24551. View

11.

Ito H, Mori K, Kagami S . Neuroimaging of stroke-like episodes in MELAS. Brain Dev. 2010; 33(4):283-8. DOI: 10.1016/j.braindev.2010.06.010. View

12.

Vanderver A, Prust M, Tonduti D, Mochel F, Hussey H, Helman G . Case definition and classification of leukodystrophies and leukoencephalopathies. Mol Genet Metab. 2015; 114(4):494-500. PMC: 4390457. DOI: 10.1016/j.ymgme.2015.01.006. View

13.

Valanne L, Ketonen L, Majander A, Suomalainen A, Pihko H . Neuroradiologic findings in children with mitochondrial disorders. AJNR Am J Neuroradiol. 1998; 19(2):369-77. PMC: 8338166. View

14.

Sijens P, Smit G, Rodiger L, van Spronsen F, Oudkerk M, Rodenburg R . MR spectroscopy of the brain in Leigh syndrome. Brain Dev. 2008; 30(9):579-83. DOI: 10.1016/j.braindev.2008.01.011. View

15.

Saneto R, Friedman S, Shaw D . Neuroimaging of mitochondrial disease. Mitochondrion. 2008; 8(5-6):396-413. PMC: 2600593. DOI: 10.1016/j.mito.2008.05.003. View

16.

Medina L, Chi T, DeVivo D, Hilal S . MR findings in patients with subacute necrotizing encephalomyelopathy (Leigh syndrome): correlation with biochemical defect. AJR Am J Roentgenol. 1990; 154(6):1269-74. DOI: 10.2214/ajr.154.6.2159689. View

17.

Lebre A, Rio M, Faivre dArcier L, Vernerey D, Landrieu P, Slama A . A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. J Med Genet. 2010; 48(1):16-23. DOI: 10.1136/jmg.2010.079624. View

18.

Lake N, Bird M, Isohanni P, Paetau A . Leigh syndrome: neuropathology and pathogenesis. J Neuropathol Exp Neurol. 2015; 74(6):482-92. DOI: 10.1097/NEN.0000000000000195. View

19.

Ohama E, OHara S, Ikuta F, Tanaka K, Nishizawa M, Miyatake T . Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuropathol. 1987; 74(3):226-33. DOI: 10.1007/BF00688185. View

20.

Kevelam S, Rodenburg R, Wolf N, Ferreira P, Lunsing R, Nijtmans L . NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology. 2013; 80(17):1577-83. PMC: 3662327. DOI: 10.1212/WNL.0b013e31828f1914. View