Combined Muscle Biopsy and Comprehensive Electrophysiology in General Anesthesia is Valuable in Diagnosis of Neuromuscular Disease in Children

Abstract

Aim The diagnostic workup in patients with delayed motor milestones suspected of having either myopathy or a congenital myasthenic syndrome is complex. Our hypothesis was that performance of a muscle biopsy and neurophysiology including stimulated single-fiber electromyography during an anesthetic procedure, combined with genetic testing has a high diagnostic quality.

Materials and Methods Clinical and paraclinical data were retrospectively collected from 24 patients aged from 1 month to 10 years (median: 5.2 years).

Results Neurophysiology examination was performed in all patients and was abnormal in 11 of 24. No patients had findings suggestive of a myasthenic syndrome. Muscle biopsy was performed in 21 of 24 and was normal in 16. Diagnostic findings included nemaline rods, inclusion bodies, fiber size variability, and type-II fiber atrophy. Genetic testing with either a gene panel or exome sequencing was performed in 18 of 24 patients, with pathogenic variants detected in ACTA1, NEB, SELENON, GRIN2B, SCN8A, and COMP genes.

Conclusion Results supporting a neuromuscular abnormality were found in 15 of 24. In six patients (25%), we confirmed a genetic diagnosis and 12 had a clinical neuromuscular diagnosis. The study suggests that combined use of neurophysiology and muscle biopsy in cases where genetic testing does not provide a diagnosis can be useful in children with delayed motor milestones and clinical evidence of a neuromuscular disease.

Keywords

children - diagnostic yield - muscle biopsy - neuromuscular disorders - single fiber electromyography

Authors' Contributions

A.P.B. and MB designed the study. M.L.B.T. and C.E.H.-H. collected the data. All authors analyzed the data and wrote the manuscript.

Publication History

Received: 19 April 2020

Accepted: 27 January 2021

Article published online:
11 March 2021

• References

• 1 Pitt MC. Nerve conduction studies and needle EMG in very small children. Eur J Paediatr Neurol 2012; 16 (03) 285-291
• 2 Pitt MC, Jabre J. The problem of lack of normative data in paediatric EMG and possible solutions. Clin Neurophysiol 2018; 129 (03) 672-675
• 3 Orhan EK, Kiraç LB, DİKmen PY. et al. Electromyography in pediatric population. Noro Psikiyatri Arsivi 2018; 55 (01) 36-39
• 4 Kinali M, Beeson D, Pitt MC. et al. Congenital myasthenic syndromes in childhood: diagnostic and management challenges. J Neuroimmunol 2008; 201-202: 6-12
• 5 García A, Calleja J, Antolín FM, Berciano J. Peripheral motor and sensory nerve conduction studies in normal infants and children. Clin Neurophysiol 2000; 111 (03) 513-520
• 6 Trontelj JV, Khuraibet A, Mihelin M. The jitter in stimulated orbicularis oculi muscle: technique and normal values. J Neurol Neurosurg Psychiatry 1988; 51 (06) 814-819
• 7 Kouyoumdjian JA, Stålberg EV. Concentric needle jitter on stimulated orbicularis oculi in 50 healthy subjects. Clin Neurophysiol 2011; 122 (03) 617-622
• 8 Richards S, Aziz N, Bale S. et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
• 9 Hafner P, Phadke R, Manzur A. et al. Electromyography and muscle biopsy in paediatric neuromuscular disorders - evaluation of current practice and literature review. Neuromuscul Disord 2019; 29 (01) 14-20
• 10 Rabie M, Jossiphov J, Nevo Y. Electromyography (EMG) accuracy compared to muscle biopsy in childhood. J Child Neurol 2007; 22 (07) 803-808