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Evoked potentials in children with oxidative metabolic defects leading to Leigh syndrome
1Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Brainstem auditory evoked potentials (BAEPs) show varied abnormalities in children with Leigh syndrome due to metabolic defects. While not specific to subgroups, BAEPs correlate with metabolic findings and clinical course.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Metabolic Disorders
Background:
- Leigh syndrome is a severe neurological disorder caused by various inherited metabolic disturbances.
- Evoked potentials are neurophysiological tests used to assess the integrity of sensory pathways in the nervous system.
- Understanding the electrophysiological correlates of Leigh syndrome can aid in diagnosis and monitoring.
Purpose of the Study:
- To investigate brainstem auditory evoked potentials (BAEPs) and other evoked potentials in children with genetically confirmed Leigh syndrome.
- To determine if specific patterns of evoked potential abnormalities correlate with different underlying metabolic deficiencies.
- To assess the utility of evoked potentials in tracking disease progression and maturational changes in Leigh syndrome.
Main Methods:
- Studied evoked potentials (BAEPs, visual, and somatosensory) in 15 children diagnosed with Leigh syndrome.
- Classified patients based on specific mitochondrial respiratory chain complex deficiencies (pyruvate dehydrogenase, complex 1, 4, or 5).
- Performed serial electrophysiological assessments in 11 children to evaluate changes over time.
Main Results:
- Abnormal BAEPs were consistently observed in pyruvate dehydrogenase deficiency and complex 4 deficiency.
- Most children with complex 1 deficiency had normal BAEPs, except for the youngest with a rapidly progressive form.
- Visual and somatosensory evoked potentials were generally abnormal but lacked specificity across subgroups; lack of normal maturation or deterioration was noted across modalities.
Conclusions:
- BAEPs show abnormalities that appear to correlate with specific metabolic defects and clinical course in Leigh syndrome.
- No single BAEP finding is pathognomonic for Leigh syndrome, but they provide valuable insights into neurological involvement.
- Evoked potential testing, particularly BAEPs, can be a useful tool for monitoring disease progression and neurological function in pediatric patients with metabolic disorders.
Abstract:
We studied evoked potentials in 15 children (age range: 2 wks to 4 yrs; mean: 10 mos) with metabolic disturbances that led to Leigh syndrome. These disturbances included deficiencies of pyruvate dehydrogenase (N = 5), complex 1 (N = 7), complex 4 or cytochrome oxidase (N = 2), and complex 5 (N = 1) deficiencies. Subsequent studies were performed in 11 children. All of the children with pyruvate dehydrogenase deficiency had abnormal brainstem auditory evoked potentials (BAEPs) due to poor morphology and reproducibility of the waveforms; central conduction time was normal in 4 of 5 initial studies. The patients with complex 4 or cytochrome oxidase deficiency had abnormal BAEPs, due to increased interpeak latencies and low amplitude or absent waves IV/V. Six of 7 of the children with complex 1 deficiency had normal BAEPs. The remaining patient (the youngest, age 6 wks) had only waves I and II bilaterally and suffered from the rapidly progressive form of complex 1 deficiency; the other 6 with complex 1 deficiency had the slowly progressive form. The one patient with complex 5 deficiency had normal BAEPs when first tested at 4 mos; abnormal BAEPs with loss of later waves were observed 10 weeks later. The visual evoked potentials and somatosensory evoked potentials usually were abnormal in these patients, but the findings were not specific to the patient subgroups. In all but one patient, subsequent studies disclosed a lack of normal maturational changes and/or deterioration across all 3 modalities. The BAEPs appeared to covary with the specific metabolic findings in these patients and with the patient's clinical course, but no BAEP could be considered characteristic of Leigh syndrome.