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A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency
  1. A S Lebre1,
  2. M Rio1,
  3. L Faivre d'Arcier1,
  4. D Vernerey1,
  5. P Landrieu2,
  6. A Slama2,
  7. C Jardel3,
  8. P Laforêt3,
  9. D Rodriguez4,
  10. N Dorison4,
  11. D Galanaud3,
  12. B Chabrol5,
  13. V Paquis-Flucklinger6,
  14. D Grévent1,
  15. S Edvardson7,
  16. J Steffann1,
  17. B Funalot8,
  18. N Villeneuve5,
  19. V Valayannopoulos1,
  20. P de Lonlay1,
  21. I Desguerre1,
  22. F Brunelle1,
  23. J P Bonnefont1,
  24. A Rötig1,
  25. A Munnich1,
  26. N Boddaert1
  1. 1Université Paris Descartes, AP-HP Hôpital Necker-Enfants Malades et Inserm U781 et U797, Départements de Génétique, de Radiologie pédiatrique et des Maladies du développement, Paris, France
  2. 2Université Paris XI, AP-HP Hôpital Bicêtre, Départements de Neurologie pédiatrique et de Biochimie, France
  3. 3AP-HP Hôpital Pitié-Salpêtrière, Départements de Biochimie et de Radiologie et Institut de myologie, Paris, France
  4. 4UPMC Univ Paris 06, AP-HP Hôpital Armand Trousseau-La Roche-Guyon et Inserm UMR 975, Département de Neuropédiatrie, Paris, France
  5. 5Université de Marseille, AP-HM Hôpital de la Timone-Enfants, Départements de Neurologie et de pédopsychiatrie pédiatrique, France
  6. 6Université de Nice Sophia Antipolis, Hôpital Archet 2, Département de Génétique Médicale, France
  7. 7Pediatric Neurology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
  8. 8Université de Limoges, Hôpital Universitaire Dupuytren, Département de Neurologie, France
  1. Correspondence to Dr Anne-Sophie Lebre, Hôpital Necker-Enfants Malades, Département de Génétique, Bâtiment Lavoisier 3è étage, 149 rue de Sèvres, Paris 75015, France; anne-sophie.lebre{at}nck.aphp.fr

Abstract

Objective To identify a consistent pattern of brain MRI imaging in primary complex I deficiency. Complex I deficiency, a major cause of respiratory chain dysfunction, accounts for various clinical presentations, including Leigh syndrome. Human complex I comprises seven core subunits encoded by mitochondrial DNA (mtDNA) and 38 core subunits encoded by nuclear DNA (nDNA). Moreover, its assembly requires six known and many unknown assembly factors. To date, no correlation between genotypes and brain MRI phenotypes has been found in complex I deficiencies.

Design and subjects The brain MRIs of 30 patients carrying known mutation(s) in genes involved in complex I were retrospectively collected and compared with the brain MRIs of 11 patients carrying known mutations in genes involved in the pyruvate dehydrogenase (PDH) complex as well as 10 patients with MT-TL1 mutations.

Results All complex I deficient patients showed bilateral brainstem lesions (30/30) and 77% (23/30) showed anomalies of the putamen. Supratentorial stroke-like lesions were only observed in complex I deficient patients carrying mtDNA mutations (8/19) and necrotising leucoencephalopathy in patients with nDNA mutations (4/5). Conversely, the isolated stroke-like images observed in patients with MT-TL1 mutations, or the corpus callosum malformations observed in PDH deficient patients, were never observed in complex I deficient patients.

Conclusion A common pattern of brain MRI imaging was identified with abnormal signal intensities in brainstem and subtentorial nuclei with lactate peak as a clue of complex I deficiency. Combining clinico-biochemical data with brain imaging may therefore help orient genetic studies in complex I deficiency.

  • Mitochondrial disorders
  • Leigh syndrome
  • MRI
  • complex I deficiency
  • diagnosis
  • metabolic disorders
  • getting research into practice
  • genetics
  • neurology

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Footnotes

  • Funding Mitocircle contract from the European commission [grant No 005260].

  • Competing interests None.

  • Patient consent Obtained. Details have been removed from these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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