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Background: Acute flaccid myelitis has emerged as the leading cause of acute flaccid paralysis in children. Acute flaccid myelitis leads to significant physical disability; hence, objective outcome measures to study disease severity and progression are desirable. In addition, nerve transfer to improve motor function in affected children needs further study., Methods: Retrospective study of acute flaccid myelitis subjects managed at Children's Healthcare of Atlanta from August 2014 to December 2019. Clinical, electromyography and nerve conduction study, neuropsychological functional independence (WeeFIM), and nerve transfer data were reviewed., Results: Fifteen children (11 boys and 4 girls) mean age 5.1±3.2 years (range 14 months to 12 years) were included. All subjects (n = 15) presented with severe asymmetric motor weakness and absent tendon reflexes. Motor nerve conduction study of the affected limbs in 93% (n = 14) showed absent or markedly reduced amplitude. Ten patients received comprehensive inpatient rehabilitation and neuropsychological evaluation. Admission and discharge WeeFIM scores showed deficits most consistent and pronounced in the domains of self-care and mobility. Multiple nerve transfer surgery was performed on 13 limbs (9 upper and 4 lower extremities) in 6 children. Postsurgery (mean duration of 10.4 ± 5.7 months) follow-up demonstrated improvement on active movement scale (AMS) in 4 subjects., Conclusion: Acute flaccid myelitis affects school-age children with asymmetric motor weakness, absent tendon reflexes, and reduced or absent motor amplitude on nerve conduction study. Comprehensive rehabilitation and nerve transfer led to improvement in motor function on neuropsychology WeeFIM and AMS scores.

Introduction: Stimulated jitter analysis (stim-JA) using a concentric needle electrode is a technique used to study the neuromuscular junction (NMJ) without voluntary activation. Our objective was to study the diagnostic sensitivity, specificity, and feasibility of stim-JA in infants and children with suspected NMJ defects., Methods: Sixteen infants and young children ages 2 months to 17 years with suspected NMJ disorders were evaluated using stim-JA over a period of 12 months., Results: Subjects with suspected NMJ defects and abnormal stim-JA subsequently had laboratory confirmation of myasthenia gravis (n = 5) and infant botulism (n = 2). Turnaround time for confirmatory laboratory tests was 6.0 ± 4.3 days, whereas stim-JA results were available immediately. All subjects tolerated stim-JA well without complications or need for sedation., Conclusions: Stim-JA is a sensitive and safe first-line diagnostic test for evaluation of suspected pediatric NMJ disorders. Stim-JA results precede assay results and may guide early treatment., (© 2015 Wiley Periodicals, Inc.)

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease. [ABSTRACT FROM AUTHOR]