Spinal Nerve Roots Abnormalities on MRI in a Child with SURF1 Mitochondrial Disease

Abstract

Variants in SURF1, encoding an assembly factor of mitochondrial respiratory chain complex IV, cause Leigh syndrome (LS) and Charcot-Marie-Tooth type 4K in children and young adolescents. Magnetic resonance imaging (MRI) appearance of enlarged nerve roots with postcontrastographic enhancement is a distinctive feature of hypertrophic neuropathy caused by onion-bulb formation and it has rarely been described in mitochondrial diseases (MDs). Spinal nerve roots abnormalities on MRI are novel findings in LS associated with variants in SURF1. Here we report detailed neuroradiological and neurophysiologic findings in a child with LS and demyelinating neuropathy SURF1-related. Our case underlines the potential contributive role of spinal neuroimaging together with neurophysiological examination to identify the full spectrum of patterns in MDs. It remains to elucidate if these observations remain peculiar of SURF1 variants or potentially detectable in other MDs with peripheral nervous system involvement.

Keywords

Leigh syndrome - spine MRI - inherited peripheral neuropathy - mitochondrial diseases - SURF1

Ethical Approval

No experimental procedure was performed, but only the investigations required by clinical practice. Therefore, it was not needed to submit the case to the approval of the Ethics Committee. Clinical investigations were conducted according to the principles expressed in Declaration of Helsinki.

Patient Consent

Informed consent was acquired from parents of the patient both for the diagnostic procedures required for diagnosis and for the use of data for scientific purposes in respect of privacy.

Authors' Contributions

A.R. and G.B. designed and conceptualized the study and drafted the manuscript. F.M., M.F.d.L., and L.R. drafted manuscript and figures. A.V. and F.M.S. reviewed and edited the manuscript. All authors have read and approved the final version of the manuscript.

^* These authors contributed equally at the work.

Publication History

Received: 21 March 2021

Accepted: 22 September 2021

Article published online:
01 December 2021

• References

• 1 Mancuso M, Orsucci D, Angelini C. et al. “Mitochondrial neuropathies”: A survey from the large cohort of the Italian Network. Neuromuscul Disord 2016; 26 (4-5): 272-276
• 2 Pareyson D, Piscosquito G, Moroni I, Salsano E, Zeviani M. Peripheral neuropathy in mitochondrial disorders. Lancet Neurol 2013; 12 (10) 1011-1024
• 3 Alves CAPF, Teixeira SR, Martin-Saavedra JS. et al. Pediatric Leigh syndrome: neuroimaging features and genetic correlations. Ann Neurol 2020; 88 (02) 218-232
• 4 Ruggiero L, Fiorillo C, Gibertini S. et al. A rare mutation in MYH7 gene occurs with overlapping phenotype. Biochem Biophys Res Commun 2015; 457 (03) 262-266
• 5 Lake NJ, Compton AG, Rahman S, Thorburn DR. Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol 2016; 79 (02) 190-203
• 6 Echaniz-Laguna A, Ghezzi D, Chassagne M. et al. SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology 2013; 81 (17) 1523-1530
• 7 Kontzialis M, Poretti A, Michell H, Bosemani T, Tekes A, Huisman TA. Spinal nerve root enhancement on MRI scans in children: a review. J Neuroimaging 2016; 26 (02) 169-179
• 8 Bayat M, Yavarian Y, Bayat A, Christensen J. Enhancement of cranial nerves, conus medullaris, and nerve roots in POLG mitochondrial disease. Neurol Genet 2019; 5 (05) e360 DOI: 10.1212/NXG.0000000000000360.
• 9 Marelli C, Salsano E, Politi LS, Labauge P. Spinal cord involvement in adult-onset metabolic and genetic diseases. J Neurol Neurosurg Psychiatry 2019; 90 (02) 211-218
• 10 Tabarki B, Hakami W, Alkhuraish N, Tlili-Graies K, Alfadhel M. Spinal cord involvement in pediatric-onset metabolic disorders with Mendelian and mitochondrial inheritance. Front Pediatr 2021; 8: 599861
• 11 van der Knaap MS, Ramesh V, Schiffmann R. et al. Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord. Neurology 2006; 66 (04) 494-498
• 12 Morana G, Biancheri R, Dirocco M. et al. Enhancing cranial nerves and cauda equina: an emerging magnetic resonance imaging pattern in metachromatic leukodystrophy and Krabbe disease. Neuropediatrics 2009; 40 (06) 291-294
• 13 Girard B, Bonnemains C, Schmitt E, Raffo E, Bilbault C. Biotinidase deficiency mimicking neuromyelitis optica beginning at the age of 4: a treatable disease. Mult Scler 2017; 23 (01) 119-122
• 14 Cellerini M, Salti S, Desideri V, Marconi G. MR imaging of the cauda equina in hereditary motor sensory neuropathies: correlations with sural nerve biopsy. AJNR Am J Neuroradiol 2000; 21 (10) 1793-1798
• 15 Santoro L, Carrozzo R, Malandrini A. et al. A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy caused by cytochrome c oxidase deficiency. Neuromuscul Disord 2000; 10 (06) 450-453